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Chatkon A, Haller KJ, Haller JP. Substitutional/positional disorder of biguanide and guanylurea in the structure of a decavanadate complex [(Bg)(HV 10O 285-)] 0.4[(HGU +)(V 10O 286-)] 0.6(H 2Met 2+) 2(H 3O +)·8H 2O. ACTA CRYSTALLOGRAPHICA SECTION B, STRUCTURAL SCIENCE, CRYSTAL ENGINEERING AND MATERIALS 2024; 80:456-466. [PMID: 39221976 DOI: 10.1107/s2052520624006929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 07/15/2024] [Indexed: 09/04/2024]
Abstract
A hydrated salt of decavanadate containing diprotonated metforminium(2+) (H2Met2+), hydronium (H3O+) and either neutral biguanide (Bg) or monoprotonated guanylurea (HGU+) exhibits a previously seen complex charge-stabilized hydrogen-bonded network [Chatkon et al. (2022). Acta Cryst. B78, 798-808]. Charge balance is achieved in two ways through substitutional disorder: a 0.6 occupied HGU+ cation is paired with a V10O286- anion, and a 0.4 occupied neutral Bg molecule is paired with a HV10O285- anion, with the remaining charge in both cases balanced by two H2Met2+ dications and one H3O+ monocation. Bg/HGU+ moieties exhibit bifurcated N-H...O hydrogen bonding to the H3O+ cation and are substitutionally/positionally disordered along with the H3O+ cation about an inversion center. The HGU+ V10O286- synthon seen in the previous study occurs again. Bg exhibits bifurcated hydrogen bonding from two amino groups to two rows of cluster O atoms running diagonally across the equatorial plane of the HV10O285- anion with a return hydrogen bond from the cluster H atom to the imino N atom of the Bg. Thus, a Bg...cluster synthon similar to the HGU+...cluster synthon previously reported is found. The disordered moieties occupy spaces with excess volume in the 3-D network structure. Interestingly, when the crystallographic unit cell of the current compound, whose X-ray data was collected at 100 K, is compared with that of a previous compound exhibiting the same supramolecular framework, unit-cell parameter c does not shorten as a and b expectantly do because of the lower data collection temperature. The lack of contraction on unit-cell parameter c is possibly due to the supramolecular structure.
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Affiliation(s)
- Aungkana Chatkon
- Chemistry Program, Faculty of Science and Technology, Nakhon Ratchasima Rajabhat University, Nakhon Ratchasima, 30000, Thailand
| | - Kenneth J Haller
- School of Chemistry, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima, 30000, Thailand
| | - Joseph P Haller
- Home School, PO Box 43, Chom Surong, Nakhon Ratchasima, 30001, Thailand
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Dumitrescu A, Maxim C, Badea M, Rostas AM, Ciorîță A, Tirsoaga A, Olar R. Decavanadate-Bearing Guanidine Derivatives Developed as Antimicrobial and Antitumor Species. Int J Mol Sci 2023; 24:17137. [PMID: 38138964 PMCID: PMC10742724 DOI: 10.3390/ijms242417137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 11/29/2023] [Accepted: 12/02/2023] [Indexed: 12/24/2023] Open
Abstract
To obtain biologically active species, a series of decavanadates (Hpbg)4[H2V10O28]·6H2O (1) (Htbg)4[H2V10O28]·6H2O; (2) (Hgnd)2(Hgnu)4[V10O28]; (3) (Hgnu)6[V10O28]·2H2O; and (4) (pbg = 1-phenyl biguanide, tbg = 1-(o-tolyl)biguanide, gnd = guanidine, and gnu = guanylurea) were synthesized and characterized by several spectroscopic techniques (IR, UV-Vis, and EPR) as well as by single crystal X-ray diffraction. Compound (1) crystallizes in space group P-1 while (3) and (4) adopt the same centrosymmetric space group P21/n. The unusual signal identified by EPR spectroscopy was assigned to a charge-transfer π(O)→d(V) process. Both stability in solution and reactivity towards reactive oxygen species (O2- and OH·) were screened through EPR signal modification. All compounds inhibited the development of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis bacterial strains in a planktonic state at a micromolar level, the most active being compound (3). However, the experiments conducted at a minimal inhibitory concentration (MIC) indicated that the compounds do not disrupt the biofilm produced by these bacterial strains. The cytotoxicity assayed against A375 human melanoma cells and BJ human fibroblasts by testing the viability, lactate dehydrogenase, and nitric oxide levels indicated compound (1) as the most active in tumor cells.
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Affiliation(s)
- Andreea Dumitrescu
- Department of Inorganic and Organic Chemistry, Biochemistry and Catalysis, Faculty of Chemistry, University of Bucharest, 90-92 Panduri Str., District 5, 050663 Bucharest, Romania; (A.D.); (C.M.); (M.B.)
| | - Catalin Maxim
- Department of Inorganic and Organic Chemistry, Biochemistry and Catalysis, Faculty of Chemistry, University of Bucharest, 90-92 Panduri Str., District 5, 050663 Bucharest, Romania; (A.D.); (C.M.); (M.B.)
| | - Mihaela Badea
- Department of Inorganic and Organic Chemistry, Biochemistry and Catalysis, Faculty of Chemistry, University of Bucharest, 90-92 Panduri Str., District 5, 050663 Bucharest, Romania; (A.D.); (C.M.); (M.B.)
| | - Arpad Mihai Rostas
- Department of Physics of Nanostructured Systems, National Institute for Research and Development of Isotopic and Molecular Technologies, 67-103 Donat Str., 400293 Cluj-Napoca, Romania;
| | - Alexandra Ciorîță
- Department of Molecular Biology and Biotechnology, Faculty of Biology and Geology, Babeș-Bolyai University, 5-7 Clinicilor St., 400001 Cluj-Napoca, Romania
| | - Alina Tirsoaga
- Department of Analytical and Physical Chemistry, Faculty of Chemistry, University of Bucharest, 4-12 Regina Elisabeta Av., District 3, 030018 Bucharest, Romania;
| | - Rodica Olar
- Department of Inorganic and Organic Chemistry, Biochemistry and Catalysis, Faculty of Chemistry, University of Bucharest, 90-92 Panduri Str., District 5, 050663 Bucharest, Romania; (A.D.); (C.M.); (M.B.)
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Amaral LMPF, Moniz T, Silva AMN, Rangel M. Vanadium Compounds with Antidiabetic Potential. Int J Mol Sci 2023; 24:15675. [PMID: 37958659 PMCID: PMC10650557 DOI: 10.3390/ijms242115675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 10/19/2023] [Accepted: 10/24/2023] [Indexed: 11/15/2023] Open
Abstract
Over the last four decades, vanadium compounds have been extensively studied as potential antidiabetic drugs. With the present review, we aim at presenting a general overview of the most promising compounds and the main results obtained with in vivo studies, reported from 1899-2023. The chemistry of vanadium is explored, discussing the importance of the structure and biochemistry of vanadate and the impact of its similarity with phosphate on the antidiabetic effect. The spectroscopic characterization of vanadium compounds is discussed, particularly magnetic resonance methodologies, emphasizing its relevance for understanding species activity, speciation, and interaction with biological membranes. Finally, the most relevant studies regarding the use of vanadium compounds to treat diabetes are summarized, considering both animal models and human clinical trials. An overview of the main hypotheses explaining the biological activity of these compounds is presented, particularly the most accepted pathway involving vanadium interaction with phosphatase and kinase enzymes involved in the insulin signaling cascade. From our point of view, the major discoveries regarding the pharmacological action of this family of compounds are not yet fully understood. Thus, we still believe that vanadium presents the potential to help in metabolic control and the clinical management of diabetes, either as an insulin-like drug or as an insulin adjuvant. We look forward to the next forty years of research in this field, aiming to discover a vanadium compound with the desired therapeutic properties.
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Affiliation(s)
- Luísa M. P. F. Amaral
- LAQV, REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, s/n, 40169-007 Porto, Portugal; (L.M.P.F.A.); (T.M.)
| | - Tânia Moniz
- LAQV, REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, s/n, 40169-007 Porto, Portugal; (L.M.P.F.A.); (T.M.)
- LAQV, REQUIMTE, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
| | - André M. N. Silva
- LAQV, REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, s/n, 40169-007 Porto, Portugal; (L.M.P.F.A.); (T.M.)
- LAQV, REQUIMTE, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
| | - Maria Rangel
- LAQV, REQUIMTE, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
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Gaique TG, Boechat SK, Neto JGO, Bento-Bernardes T, Medeiros RF, Pazos-Moura CC, Oliveira KJ. Cinnamaldehyde supplementation acts as an insulin mimetic compound improving glucose metabolism during adolescence, but not during adulthood, in healthy male rats. Hormones (Athens) 2023; 22:295-304. [PMID: 36810755 DOI: 10.1007/s42000-023-00442-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 02/10/2023] [Indexed: 02/23/2023]
Abstract
PURPOSE Adolescence is a critical period of increased vulnerability to nutritional modifications, and adolescents may respond differently from adults to dietary intake and nutraceuticals. Cinnamaldehyde, a major bioactive compound of cinnamon, improves energy metabolism, as has been shown in studies conducted primarily in adult animals. We hypothesized that cinnamaldehyde treatment may have a higher impact on the glycemic homeostasis of healthy adolescent rats than on healthy adult rats. METHODS Male adolescent (30 days) or adult (90 days) Wistar rats received cinnamaldehyde (40 mg/kg) for 28 days by gavage. The oral glucose tolerance test (OGTT), liver glycogen content, serum insulin concentration, serum lipid profile, and hepatic insulin signaling marker expression were evaluated. RESULTS Cinnamaldehyde-treated adolescent rats showed less weight gain (P = 0.041), improved OGTT (P = 0.004), increased expression of phosphorylated IRS-1 (P = 0.015), and a trend to increase phosphorylated IRS-1 (P = 0.063) in the liver of adolescent rats in the basal state. None of these parameters was modified after treatment with cinnamaldehyde in the adult group. Cumulative food intake, visceral adiposity, liver weight, serum insulin, serum lipid profile, hepatic glycogen content, and liver protein expression of IRβ, phosphorylated IRβ, AKT, phosphorylated AKT, and PTP-1B in the basal state were similar between both age groups. CONCLUSION In a healthy metabolic condition, cinnamaldehyde supplementation affects glycemic metabolism in adolescent rats while promoting no changes in adult rats.
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Affiliation(s)
- Thaiane G Gaique
- Departamento de Fisiologia e Farmacologia, Universidade Federal Fluminense, Niterói, RJ, 24210-130, Brazil
| | - Silvia K Boechat
- Departamento de Fisiologia e Farmacologia, Universidade Federal Fluminense, Niterói, RJ, 24210-130, Brazil
| | - Jessika Geisebel O Neto
- Departamento de Fisiologia e Farmacologia, Universidade Federal Fluminense, Niterói, RJ, 24210-130, Brazil
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | - Thais Bento-Bernardes
- Departamento de Fisiologia e Farmacologia, Universidade Federal Fluminense, Niterói, RJ, 24210-130, Brazil
| | - Renata F Medeiros
- Departamento de Fisiologia e Farmacologia, Universidade Federal Fluminense, Niterói, RJ, 24210-130, Brazil
| | - Carmen C Pazos-Moura
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | - Karen J Oliveira
- Departamento de Fisiologia e Farmacologia, Universidade Federal Fluminense, Niterói, RJ, 24210-130, Brazil.
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Carpéné C, Viana P, Iffiú-Soltesz Z, Tapolcsányi P, Földi AÁ, Mátyus P, Dunkel P. Effects of Chemical Structures Interacting with Amine Oxidases on Glucose, Lipid and Hydrogen Peroxide Handling by Human Adipocytes. Molecules 2022; 27:6224. [PMID: 36234761 PMCID: PMC9571511 DOI: 10.3390/molecules27196224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 09/07/2022] [Accepted: 09/19/2022] [Indexed: 11/26/2022] Open
Abstract
Benzylamine is a natural molecule present in food and edible plants, capable of activating hexose uptake and inhibiting lipolysis in human fat cells. These effects are dependent on its oxidation by amine oxidases present in adipocytes, and on the subsequent hydrogen peroxide production, known to exhibit insulin-like actions. Virtually, other substrates interacting with such hydrogen peroxide-releasing enzymes potentially can modulate lipid accumulation in adipose tissue. Inhibition of such enzymes has also been reported to influence lipid deposition. We have therefore studied in human adipocytes the lipolytic and lipogenic activities of pharmacological entities designed to interact with amine oxidases highly expressed in this cell type: the semicarbazide-sensitive amine oxidase (SSAO also known as PrAO or VAP-1) and the monoamine oxidases (MAO). The results showed that SZV-2016 and SZV-2017 behaved as better substrates than benzylamine, releasing hydrogen peroxide once oxidized, and reproduced or even exceeded its insulin-like metabolic effects in fat cells. Additionally, several novel SSAO inhibitors, such as SZV-2007 and SZV-1398, have been evidenced and shown to inhibit benzylamine metabolic actions. Taken as a whole, our findings reinforce the list of molecules that influence the regulation of triacylglycerol assembly/breakdown, at least in vitro in human adipocytes. The novel compounds deserve deeper investigation of their mechanisms of interaction with SSAO or MAO, and constitute potential candidates for therapeutic use in obesity and diabetes.
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Affiliation(s)
- Christian Carpéné
- Institut des Maladies Métaboliques et Cardiovasculaires, INSERM UMR1297, 31432 Toulouse, France
- Team Dinamix, Institute of Metabolic and Cardiovascular Diseases (I2MC), Paul Sabatier University, 31432 Toulouse, France
| | - Pénélope Viana
- Institut des Maladies Métaboliques et Cardiovasculaires, INSERM UMR1297, 31432 Toulouse, France
- Team Dinamix, Institute of Metabolic and Cardiovascular Diseases (I2MC), Paul Sabatier University, 31432 Toulouse, France
| | - Zsuzsa Iffiú-Soltesz
- Institut des Maladies Métaboliques et Cardiovasculaires, INSERM UMR1297, 31432 Toulouse, France
| | - Pál Tapolcsányi
- Department of Organic Chemistry, Semmelweis University, H-1092 Budapest, Hungary
| | - Anna Ágota Földi
- Department of Organic Chemistry, Semmelweis University, H-1092 Budapest, Hungary
| | - Péter Mátyus
- Department of Organic Chemistry, Semmelweis University, H-1092 Budapest, Hungary
- E-Group ICT SOFTWARE, H-1027 Budapest, Hungary
| | - Petra Dunkel
- Department of Organic Chemistry, Semmelweis University, H-1092 Budapest, Hungary
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Aureliano M, Gumerova NI, Sciortino G, Garribba E, McLauchlan CC, Rompel A, Crans DC. Polyoxidovanadates' interactions with proteins: An overview. Coord Chem Rev 2022; 454:214344. [DOI: 10.1016/j.ccr.2021.214344] [Citation(s) in RCA: 74] [Impact Index Per Article: 24.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Corona-Motolinia ND, Martínez-Valencia B, Noriega L, Sánchez-Gaytán BL, Melendez FJ, García-García A, Choquesillo-Lazarte D, Rodríguez-Diéguez A, Castro ME, González-Vergara E. Tris(2-Pyridylmethylamine)V(O)2 Complexes as Counter Ions of Diprotonated Decavanadate Anion: Potential Antineoplastic Activity. Front Chem 2022; 10:830511. [PMID: 35252118 PMCID: PMC8888438 DOI: 10.3389/fchem.2022.830511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 01/17/2022] [Indexed: 11/18/2022] Open
Abstract
The synthesis and theoretical-experimental characterization of a novel diprotanated decavanadate is presented here due to our search for novel anticancer metallodrugs. Tris(2-pyridylmethyl)amine (TPMA), which is also known to have anticancer activity in osteosarcoma cell lines, was introduced as a possible cationic species that could act as a counterpart for the decavanadate anion. However, the isolated compound contains the previously reported vanadium (V) dioxido-tpma moieties, and the decavanadate anion appears to be diprotonated. The structural characterization of the compound was performed by infrared spectroscopy and single-crystal X-ray diffraction. In addition, DFT calculations were used to analyze the reactive sites involved in the donor-acceptor interactions from the molecular electrostatic potential maps. The level of theory mPW1PW91/6–31G(d)-LANL2DZ and ECP = LANL2DZ for the V atom was used. These insights about the compounds’ main interactions were supported by analyzing the noncovalent interactions utilizing the AIM and Hirshfeld surfaces approach. Molecular docking studies with small RNA fragments were used to assess the hypothesis that decavanadate’s anticancer activity could be attributed to its interaction with lncRNA molecules. Thus, a combination of three potentially beneficial components could be evaluated in various cancer cell lines.
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Affiliation(s)
- Nidia D. Corona-Motolinia
- Centro de Química del Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico
| | - Beatriz Martínez-Valencia
- Centro de Química del Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico
| | - Lisset Noriega
- Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico
| | - Brenda L. Sánchez-Gaytán
- Centro de Química del Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico
| | - Francisco J. Melendez
- Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico
| | - Amalia García-García
- Departamento de Química Inorgánica, Facultad de Ciencias, Universidad de Granada, Granada, Spain
| | | | | | - María Eugenia Castro
- Centro de Química del Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico
- *Correspondence: María Eugenia Castro, ; Enrique González-Vergara,
| | - Enrique González-Vergara
- Centro de Química del Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico
- *Correspondence: María Eugenia Castro, ; Enrique González-Vergara,
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Aureliano M, Gumerova NI, Sciortino G, Garribba E, Rompel A, Crans DC. Polyoxovanadates with emerging biomedical activities. Coord Chem Rev 2021; 447:214143. [DOI: 10.1016/j.ccr.2021.214143] [Citation(s) in RCA: 120] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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2-Aminopyrimidinium Decavanadate: Experimental and Theoretical Characterization, Molecular Docking, and Potential Antineoplastic Activity. INORGANICS 2021. [DOI: 10.3390/inorganics9090067] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
The interest in decavanadate anions has increased in recent decades, since these clusters show interesting applications as varied as sensors, batteries, catalysts, or new drugs in medicine. Due to the capacity of the interaction of decavanadate with a variety of biological molecules because of its high negative charge and oxygen-rich surface, this cluster is being widely studied both in vitro and in vivo as a treatment for several global health problems such as diabetes mellitus, cancer, and Alzheimer’s disease. Here, we report a new decavanadate compound with organic molecules synthesized in an aqueous solution and structurally characterized by elemental analysis, infrared spectroscopy, thermogravimetric analysis, and single-crystal X-ray diffraction. The decavanadate anion was combined with 2-aminopyrimidine to form the compound [2-ampymH]6[V10O28]·5H2O (1). In the crystal lattice, organic molecules are stacked by π–π interactions, with a centroid-to-centroid distance similar to that shown in DNA or RNA molecules. Furthermore, computational DFT calculations of Compound 1 corroborate the hydrogen bond interaction between pyrimidine molecules and decavanadate anions, as well as the π–π stacking interactions between the central pyrimidine molecules. Finally, docking studies with test RNA molecules indicate that they could serve as other potential targets for the anticancer activity of decavanadate anion.
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Sarmiento-Ortega VE, Moroni-González D, Díaz A, Morán C, Brambila E, Treviño S. Sodium metavanadate treatment improves glycogen levels in multiple tissues in a model of metabolic syndrome caused by chronic cadmium exposure in Wistar rats. Biometals 2021; 34:245-258. [PMID: 33389338 DOI: 10.1007/s10534-020-00276-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 11/27/2020] [Indexed: 11/24/2022]
Abstract
Cadmium, one of the more hazardous environmental contaminants, has been proposed as a metabolic disruptor. Vanadium has emerged as a possible treatment for metabolic diseases. Both metals are important in public health. We aimed to investigate whether vanadium treatment is effective against metabolic disturbances caused by chronic exposure to the lowest-observable adverse effect level of cadmium. Male Wistar rats were exposed to cadmium (32.5 ppm) in drinking water for 3 months. Metabolic complications such as overweight, visceral adipose gain, hyperglycemia, impaired glucose tolerance, and dyslipidemia were detected, and low glycogen levels and steatosis were observed in the tissues. Then, the control and treated animals were subdivided and treated with a solution of 5 μM NaVO3/kg/twice a week for 2 months. The control-NaVO3 group did not show zoometric or metabolic changes. A strong interaction of NaVO3 treatment over cadmium metabolic disruption was observed. The vanadium accumulation diminished cadmium concentration in tissues. Also, vanadium interaction improved glucose homeostasis. The major effect was observed on glycogen synthesis, which was fully recovered in all tissues analyzed. Additionally, vanadium treatment prevented overweight and visceral fat accumulation, improving BMI and the percentage of fat. However, NaVO3 treatment did not have an effect on dyslipidemia or steatosis. In conclusion, this work shows that vanadium administration has a strong effect against metabolic disturbances caused by chronic cadmium exposure, observing powerful interaction on glucose homeostasis.
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Affiliation(s)
- Victor Enrique Sarmiento-Ortega
- Laboratory of Chemical-Clinical Investigations, Department of Clinical Chemistry, Faculty of Chemistry Science, University Autonomous of Puebla, 14 South. FCQ1, University City, C.P. 72560, Puebla, Mexico
| | - Diana Moroni-González
- Laboratory of Chemical-Clinical Investigations, Department of Clinical Chemistry, Faculty of Chemistry Science, University Autonomous of Puebla, 14 South. FCQ1, University City, C.P. 72560, Puebla, Mexico
| | - Alfonso Díaz
- Department of Pharmacy, Faculty of Chemistry Science, University Autonomous of Puebla, 22 South. FC91, University City, C.P. 72560, Puebla, Mexico
| | - Carolina Morán
- Department of Biology and Reproduction Toxicology, Science Institute, University Autonomous of Puebla, 14 South. University City, C.P. 72560, Puebla, Mexico
| | - Eduardo Brambila
- Laboratory of Chemical-Clinical Investigations, Department of Clinical Chemistry, Faculty of Chemistry Science, University Autonomous of Puebla, 14 South. FCQ1, University City, C.P. 72560, Puebla, Mexico
| | - Samuel Treviño
- Laboratory of Chemical-Clinical Investigations, Department of Clinical Chemistry, Faculty of Chemistry Science, University Autonomous of Puebla, 14 South. FCQ1, University City, C.P. 72560, Puebla, Mexico.
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Morsy MD, Bin-Jaliah I, Bashir SO, Shatoor A, Haidara MA. The impact of concomitant administration of vanadium and insulin on endothelial dysfunction markers (PAI-1 and ET-1) in type 1 diabetic rats. Arch Physiol Biochem 2021; 127:20-27. [PMID: 30789058 DOI: 10.1080/13813455.2019.1573840] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Revised: 12/05/2018] [Accepted: 12/15/2018] [Indexed: 02/08/2023]
Abstract
Endothelial dysfunction in type 1 diabetes mellitus (T1DM) is an important factor in the pathogenesis of micro- and macrovascular complications. The present study was to investigate the impact of combined vanadium and insulin for proper control and protection against endothelial dysfunction in T1DM rats. Sixty male Sprague-Dawley rats were randomly divided into six groups; control non-treated; control vanadium treated; T1DM; T1DM + insulin; T1DM + vanadium; T1DM + insulin + vanadium treated groups. At the end of the experiment (6 weeks), serum C-reactive protein, tumour necrosis factor-alpha, IL-6, endothelin-1, plasminogen activator inhibitor-1, fasting glucose serum lipogram, liver homogenate SOD activity and MDA levels were determined. Concomitant insulin and vanadium treatment improved the diabetic metabolic disturbances in addition to endothelial dysfunction and inflammatory markers. We can conclude that concomitant administration of both vanadium and insulin in T1DM decreased the risk for the development of endothelial dysfunction, micro- and macrovascular complications.
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Affiliation(s)
- M D Morsy
- Department of Physiology, College of Medicine, King Khalid University, Abha, Saudi Arabia
- Department of Physiology, College of Medicine, Menoufia University, Shebeen Alkoom, Egypt
| | - I Bin-Jaliah
- Department of Physiology, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - S O Bashir
- Department of Physiology, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - A Shatoor
- Department of Cardiology, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - M A Haidara
- Department of Physiology, College of Medicine, King Khalid University, Abha, Saudi Arabia
- Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt
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Chen X, Daniels NA, Cottrill D, Cao Y, Wang X, Li Y, Shriwas P, Qian Y, Archer MW, Whitticar NB, Jahan I, Nunemaker CS, Guo A. Natural Compound α-PGG and Its Synthetic Derivative 6Cl-TGQ Alter Insulin Secretion: Evidence for Diminishing Glucose Uptake as a Mechanism. Diabetes Metab Syndr Obes 2021; 14:759-772. [PMID: 33658814 PMCID: PMC7917315 DOI: 10.2147/dmso.s284295] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Accepted: 12/24/2020] [Indexed: 12/17/2022] Open
Abstract
PURPOSE Previously we showed that natural compound α-penta-galloyl-glucose (α-PGG) and its synthetic derivative 6-chloro-6-deoxy-1,2,3,4-tetra-O-galloyl-α-D-glucopyranose (6Cl-TGQ) act to improve insulin signaling in adipocytes by increasing glucose transport. In this study, we investigated the mechanism of actions of α-PGG and 6Cl-TGQ on insulin secretion. METHODS Mouse islets and/or INS-1832/13 beta-cells were used to test the effects of our compounds on glucose-stimulated insulin secretion (GSIS), intracellular calcium [Ca2+]i using fura-2AM, glucose transport activity via a radioactive glucose uptake assay, intracellular ATP/ADP, and extracellular acidification (ECAR) and mitochondrial oxygen consumption rates (OCAR) using Seahorse metabolic analysis. RESULTS Both compounds reduced GSIS in beta-cells without negatively affecting cell viability. The compounds primarily diminished glucose uptake into islets and beta-cells. Despite insulin-like effects in the peripheral tissues, these compounds do not act through the insulin receptor in islets. Further interrogation of the stimulus-secretion pathway showed that all the key metabolic factors involved in GSIS including ECAR, OCAR, ATP/ADP ratios, and [Ca2+]i of INS-1832/13 cells were diminished after the compound treatment. CONCLUSION The compounds suppress glucose uptake of the beta-cells, which consequently slows down the rates of glycolysis and ATP synthesis, leading to decrease in [Ca2+]i and GSIS. The difference between adipocytes and beta-cells in effects on glucose uptake is of great interest. Further structural and functional modifications could produce new compounds with optimized therapeutic potentials for different target cells. The higher potency of synthetic 6Cl-TGQ in enhancing insulin signaling in adipocytes but lower potency in reducing glucose uptake in beta-cells compared to α-PGG suggests the feasibility of such an approach.
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Affiliation(s)
- Xiaozhuo Chen
- The Diabetes Institute at Ohio University, Athens, OH, 45701, USA
- The Edison Biotechnology Institute, Athens, OH, 45701, USA
- Department of Biological Sciences, Athens, OH, 45701, USA
- Department of Biomedical Sciences, Athens, OH, 45701, USA
- Heritage College of Osteopathic Medicine, Athens, OH, 45701, USA
- Interdisciplinary Graduate Program in Molecular and Cellular Biology, Athens, OH, 45701, USA
- Department of Chemistry and Biochemistry, Athens, OH, 45701, USA
| | - Nigel A Daniels
- The Diabetes Institute at Ohio University, Athens, OH, 45701, USA
- Department of Biomedical Sciences, Athens, OH, 45701, USA
- Heritage College of Osteopathic Medicine, Athens, OH, 45701, USA
- Department of Specialty Medicine, Athens, OH, 45701, USA
| | - David Cottrill
- The Edison Biotechnology Institute, Athens, OH, 45701, USA
- Department of Biological Sciences, Athens, OH, 45701, USA
| | - Yanyang Cao
- The Edison Biotechnology Institute, Athens, OH, 45701, USA
- Department of Biological Sciences, Athens, OH, 45701, USA
| | - Xuan Wang
- The Edison Biotechnology Institute, Athens, OH, 45701, USA
- Department of Biological Sciences, Athens, OH, 45701, USA
| | - Yunsheng Li
- The Edison Biotechnology Institute, Athens, OH, 45701, USA
| | - Pratik Shriwas
- The Edison Biotechnology Institute, Athens, OH, 45701, USA
- Department of Biological Sciences, Athens, OH, 45701, USA
| | - Yanrong Qian
- The Edison Biotechnology Institute, Athens, OH, 45701, USA
| | - Michael W Archer
- The Diabetes Institute at Ohio University, Athens, OH, 45701, USA
- Department of Biomedical Sciences, Athens, OH, 45701, USA
| | - Nicholas B Whitticar
- Department of Biomedical Sciences, Athens, OH, 45701, USA
- Translational Biomedical Sciences Program, Ohio University, Athens, OH, 45701, USA
| | - Ishrat Jahan
- The Diabetes Institute at Ohio University, Athens, OH, 45701, USA
- Department of Biomedical Sciences, Athens, OH, 45701, USA
| | - Craig S Nunemaker
- The Diabetes Institute at Ohio University, Athens, OH, 45701, USA
- Department of Biological Sciences, Athens, OH, 45701, USA
- Department of Biomedical Sciences, Athens, OH, 45701, USA
- Heritage College of Osteopathic Medicine, Athens, OH, 45701, USA
- Craig S Nunemaker Department of Biomedical Sciences, 1 Ohio University, Athens, OH, 45701, USATel +1 740-593-2387Fax +1 740-593-4795 Email
| | - Aili Guo
- Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, University of California at Davis (UC Davis) School of Medicine, UC Davis Health Science, Sacramento, CA, 95817, USA
- Correspondence: Aili Guo Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, University of California at Davis (UC Davis) School of Medicine, UC Davis Health Science, PSSB, G400, 4150 V St., Sacramento, CA, 95817, USATel +1 916-734-3730Fax +1 916-734-2292 Email
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Fontaine J, Tavernier G, Morin N, Carpéné C. Vanadium-dependent activation of glucose transport in adipocytes by catecholamines is not mediated via adrenoceptor stimulation or monoamine oxidase activity. World J Diabetes 2020; 11:622-643. [PMID: 33384769 PMCID: PMC7754167 DOI: 10.4239/wjd.v11.i12.622] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 10/12/2020] [Accepted: 10/26/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Benzylamine and methylamine activate glucose uptake in adipocytes. For tyramine, this effect has even been extended to cardiomyocytes. AIM To investigate the effects of catecholamines and other amines on glucose uptake. METHODS A screening compared 25 biogenic amines on 2-deoxyglucose (2-DG) uptake activation in rat adipocytes. Pharmacological approaches and transgenic mouse models were then used to decipher the mode of action of several hits. RESULTS In rat adipocytes, insulin stimulation of 2-DG uptake was reproduced with catecholamines. 100 µmol/L or 1 mmol/L adrenaline, noradrenaline, dopamine and deoxyepinephrine, maximally activated hexose transport only when sodium orthovanadate was added at 100 µmol/L. Such activation was similar to that already reported for benzylamine, methylamine and tyramine, well-recognized substrates of semicarbazide-sensitive amine oxidase (SSAO) and monoamine oxidase (MAO). Several, but not all, tested agonists of β-adrenoreceptors (β-ARs) also activated glucose transport while α-AR agonists were inactive. Lack of blockade by α- and β-AR antagonists indicated that catecholamine-induced 2-DG uptake was not mediated by AR stimulation. Adipocytes from mice lacking β1-, β2- and β3-ARs (triple KO) also responded to millimolar doses of adrenaline or noradrenaline by activating hexose transport in the presence of 100 µmol/L vanadate. The MAO blocker pargyline, and SSAO inhibitors did not block the effects of adrenaline or noradrenaline plus vanadate, which were blunted by antioxidants. CONCLUSION Catecholamines exert unexpected insulin-like actions in adipocytes when combined with vanadium. For limiting insulin resistance by activating glucose consumption at least in fat stores, we propose that catecholamine derivatives combined with vanadium can generate novel complexes that may have low toxicity and promising anti-diabetic properties.
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Affiliation(s)
- Jessica Fontaine
- Institut des Maladies Métaboliques et Cardiovasculaires, Institut National de la Santé et de la Recherche Médicale, INSERM UMR1048, Université Paul Sabatier Toulouse III, Toulouse 31432, France
| | - Geneviève Tavernier
- Institut des Maladies Métaboliques et Cardiovasculaires, Institut National de la Santé et de la Recherche Médicale, INSERM UMR1048, Université Paul Sabatier Toulouse III, Toulouse 31432, France
| | - Nathalie Morin
- Institut des Maladies Métaboliques et Cardiovasculaires, Institut National de la Santé et de la Recherche Médicale, INSERM UMR1048, Université Paul Sabatier Toulouse III, Toulouse 31432, France
- INSERM UMR 1139 Faculté de Pharmacie, Université de Paris, Paris 75006, France
| | - Christian Carpéné
- Institut des Maladies Métaboliques et Cardiovasculaires, Institut National de la Santé et de la Recherche Médicale, INSERM UMR1048, Université Paul Sabatier Toulouse III, Toulouse 31432, France
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Treviño S, Diaz A. Vanadium and insulin: Partners in metabolic regulation. J Inorg Biochem 2020; 208:111094. [PMID: 32438270 DOI: 10.1016/j.jinorgbio.2020.111094] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 04/18/2020] [Accepted: 04/21/2020] [Indexed: 12/12/2022]
Abstract
Since the 1970s, the biological role of vanadium compounds has been discussed as insulin-mimetic or insulin-enhancer agents. The action of vanadium compounds has been investigated to determine how they influence the insulin signaling pathway. Khan and coworkers proposed key proteins for the insulin pathway study, introducing the concept "critical nodes". In this review, we also considered critical kinases and phosphatases that participate in this pathway, which will permit a better comprehension of a critical node, where vanadium can act: a) insulin receptor, insulin receptor substrates, and protein tyrosine phosphatases; b) phosphatidylinositol 3'-kinase, 3-phosphoinositide-dependent protein kinase and mammalian target of rapamycin complex, protein kinase B, and phosphatase and tensin homolog; and c) insulin receptor substrates and mitogen-activated protein kinases, each node having specific negative modulators. Additionally, leptin signaling was considered because together with insulin, it modulates glucose and lipid homeostasis. Even in recent literature, the possibility of vanadium acting against metabolic diseases or cancer is confirmed although the mechanisms of action are not well understood because these critical nodes have not been systematically investigated. Through this review, we establish that vanadium compounds mainly act as phosphatase inhibitors and hypothesize on their capacity to affect kinases, which are critical to other hormones that also act on common parts of the insulin pathway.
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Affiliation(s)
- Samuel Treviño
- Laboratory of Chemical-Clinical Investigations, Department of Clinical Chemistry, Faculty of Chemistry Science, University Autonomous of Puebla, 14 South. FCQ1, University City, Puebla, C.P. 72560, Mexico.
| | - Alfonso Diaz
- Department of Pharmacy, Faculty of Chemistry Science, University Autonomous of Puebla, 22 South, FCQ9, University City, Puebla, C.P. 72560, Mexico.
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Xie J, Wang S, Ma P, Ma F, Li J, Wang W, Lu F, Xiong H, Gu Y, Zhang S, Xu H, Yang G, Lerner RA. Selection of Small Molecules that Bind to and Activate the Insulin Receptor from a DNA-Encoded Library of Natural Products. iScience 2020; 23:101197. [PMID: 32544667 PMCID: PMC7298650 DOI: 10.1016/j.isci.2020.101197] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 02/21/2020] [Accepted: 05/21/2020] [Indexed: 12/11/2022] Open
Abstract
Although insulin is a life-saving medicine, administration by daily injection remains problematic. Our goal was to exploit the power of DNA-encoded libraries to identify molecules with insulin-like activity but with the potential to be developed as oral drugs. Our strategy involved using a 104-member DNA-encoded library containing 160 Traditional Chinese Medicines (nDEL) to identify molecules that bind to and activate the insulin receptor. Importantly, we used the natural ligand, insulin, to liberate bound molecules. Using this selection method on our relatively small, but highly diverse, nDEL yielded a molecule capable of both binding to and activating the insulin receptor. Chemical analysis showed this molecule to be a polycyclic analog of the guanidine metformin, a known drug used to treat diabetes. By using our protocol with other, even larger, DELs we can expect to identify additional organic molecules capable of binding to and activating the insulin receptor.
Annotation of natural products via complementary bifunctional linkers Function-guided DEL selection using the natural ligand for competitive elution Identification of Rutaecarpine as a binder and activator of insulin receptor
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Affiliation(s)
- Jia Xie
- Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037, USA
| | - Shuyue Wang
- Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Peixiang Ma
- Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China
| | - Fei Ma
- Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037, USA
| | - Jie Li
- Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Wei Wang
- Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China
| | - Fengping Lu
- Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China
| | - Huan Xiong
- Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China
| | - Yuang Gu
- Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Shuning Zhang
- Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Hongtao Xu
- Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China.
| | - Guang Yang
- Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China.
| | - Richard A Lerner
- Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037, USA.
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Chan CB, Ahuja P, Ye K. Developing Insulin and BDNF Mimetics for Diabetes Therapy. Curr Top Med Chem 2019; 19:2188-2204. [PMID: 31660832 DOI: 10.2174/1568026619666191010160643] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Revised: 08/29/2019] [Accepted: 09/05/2019] [Indexed: 01/06/2023]
Abstract
Diabetes is a global public health concern nowadays. The majority of diabetes mellitus (DM) patients belong to type 2 diabetes mellitus (T2DM), which is highly associated with obesity. The general principle of current therapeutic strategies for patients with T2DM mainly focuses on restoring cellular insulin response by potentiating the insulin-induced signaling pathway. In late-stage T2DM, impaired insulin production requires the patients to receive insulin replacement therapy for maintaining their glucose homeostasis. T2DM patients also demonstrate a drop of brain-derived neurotrophic factor (BDNF) in their circulation, which suggests that replenishing BDNF or enhancing its downstream signaling pathway may be beneficial. Because of their protein nature, recombinant insulin or BDNF possess several limitations that hinder their clinical application in T2DM treatment. Thus, developing orally active "insulin pill" or "BDNF pill" is essential to provide a more convenient and effective therapy. This article reviews the current development of non-peptidyl chemicals that mimic insulin or BDNF and their potential as anti-diabetic agents.
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Affiliation(s)
- Chi Bun Chan
- School of Biological Sciences, The University of Hong Kong, Hong Kong
| | - Palak Ahuja
- School of Biological Sciences, The University of Hong Kong, Hong Kong
| | - Keqiang Ye
- Department of Pathology and Laboratory Medicine, Emory University of School of Medicine, Atlanta, GA, United States
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Peng Y, Sun Q, Park Y. Chicoric acid promotes glucose uptake and Akt phosphorylation via AMP-activated protein kinase α-dependent pathway. J Funct Foods 2019. [DOI: 10.1016/j.jff.2019.05.020] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
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Moreira LDPD, Gomes JVP, Mattar JB, Chaves LO, Martino HSD. Potential of trace elements as supplements for the metabolic control of Type 2 Diabetes Mellitus: A systematic review. J Funct Foods 2019. [DOI: 10.1016/j.jff.2019.04.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
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Abstract
Ultra-trace elements or occasionally beneficial elements (OBE) are the new categories of minerals including vanadium (V). The importance of V is attributed due to its multifaceted biological roles, i.e., glucose and lipid metabolism as an insulin-mimetic, antilipemic and a potent stress alleviating agent in diabetes when vanadium is administered at lower doses. It competes with iron for transferrin (binding site for transportation) and with lactoferrin as it is secreted in milk also. The intracellular enzyme protein tyrosine phosphatase, causing the dephosphorylation at beta subunit of the insulin receptor, is inhibited by vanadium, thus facilitating the uptake of glucose inside the cell but only in the presence of insulin. Vanadium could be useful as a potential immune-stimulating agent and also as an antiinflammatory therapeutic metallodrug targeting various diseases. Physiological state and dose of vanadium compounds hold importance in causing toxicity also. Research has been carried out mostly on laboratory animals but evidence for vanadium importance as a therapeutic agent are available in humans and large animals also. This review examines the potential biochemical and molecular role, possible kinetics and distribution, essentiality, immunity, and toxicity-related study of vanadium in a biological system.
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Affiliation(s)
| | - Veena Mani
- National Dairy Research Institute, Karnal, Haryana, India
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Panchal SK, Wanyonyi S, Brown L. Selenium, Vanadium, and Chromium as Micronutrients to Improve Metabolic Syndrome. Curr Hypertens Rep 2017; 19:10. [PMID: 28197835 DOI: 10.1007/s11906-017-0701-x] [Citation(s) in RCA: 65] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Trace metals play an important role in the proper functioning of carbohydrate and lipid metabolism. Some of the trace metals are thus essential for maintaining homeostasis, while deficiency of these trace metals can cause disorders with metabolic and physiological imbalances. This article concentrates on three trace metals (selenium, vanadium, and chromium) that may play crucial roles in controlling blood glucose concentrations possibly through their insulin-mimetic effects. For these trace metals, the level of evidence available for their health effects as supplements is weak. Thus, their potential is not fully exploited for the target of metabolic syndrome, a constellation that increases the risk for cardiovascular disease and type 2 diabetes. Given that the prevalence of metabolic syndrome is increasing throughout the world, a simpler option of interventions with food supplemented with well-studied trace metals could serve as an answer to this problem. The oxidation state and coordination chemistry play crucial roles in defining the responses to these trace metals, so further research is warranted to understand fully their metabolic and cardiovascular effects in human metabolic syndrome.
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Affiliation(s)
- Sunil K Panchal
- Institute for Agriculture and the Environment, University of Southern Queensland, QLD, Toowoomba, 4350, Australia
| | - Stephen Wanyonyi
- Institute for Agriculture and the Environment, University of Southern Queensland, QLD, Toowoomba, 4350, Australia
| | - Lindsay Brown
- Institute for Agriculture and the Environment, University of Southern Queensland, QLD, Toowoomba, 4350, Australia.
- School of Health and Wellbeing, University of Southern Queensland, QLD, Toowoomba, 4350, Australia.
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Ye L, Maji S, Sanghera N, Gopalasingam P, Gorbunov E, Tarasov S, Epstein O, Klein-Seetharaman J. Structure and dynamics of the insulin receptor: implications for receptor activation and drug discovery. Drug Discov Today 2017; 22:1092-1102. [PMID: 28476537 DOI: 10.1016/j.drudis.2017.04.011] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2016] [Revised: 04/16/2017] [Accepted: 04/19/2017] [Indexed: 01/05/2023]
Abstract
Recently, major progress has been made in uncovering the mechanisms of how insulin engages its receptor and modulates downstream signal transduction. Here, we present in detail the current structural knowledge surrounding the individual components of the complex, binding sites, and dynamics during the activation process. A novel kinase triggering mechanism, the 'bow-arrow model', is proposed based on current knowledge and computational simulations of this system, in which insulin, after its initial interaction with binding site 1, engages with site 2 between the fibronectin type III (FnIII)-1 and -2 domains, which changes the conformation of FnIII-3 and eventually translates into structural changes across the membrane. This model provides a new perspective on the process of insulin binding to its receptor and, thus, could lead to future novel drug discovery efforts.
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Affiliation(s)
- Libin Ye
- Department of Structural Biology, University of Pittsburgh, Pittsburgh, PA 15260, USA
| | - Suvrajit Maji
- Department of Structural Biology, University of Pittsburgh, Pittsburgh, PA 15260, USA
| | - Narinder Sanghera
- Division of Metabolic and Vascular Health & Systems, Medical School, University of Warwick, Coventry CV4 7AL, UK
| | - Piraveen Gopalasingam
- Division of Metabolic and Vascular Health & Systems, Medical School, University of Warwick, Coventry CV4 7AL, UK
| | - Evgeniy Gorbunov
- OOO 'NPF 'MATERIA MEDICA HOLDING', 47-1, Trifonovskaya St, Moscow 129272, Russian Federation
| | - Sergey Tarasov
- OOO 'NPF 'MATERIA MEDICA HOLDING', 47-1, Trifonovskaya St, Moscow 129272, Russian Federation
| | - Oleg Epstein
- The Institute of General Pathology and Pathophysiology, 8, Baltiyskaya St, 125315 Moscow, Russian Federation
| | - Judith Klein-Seetharaman
- Department of Structural Biology, University of Pittsburgh, Pittsburgh, PA 15260, USA; Division of Metabolic and Vascular Health & Systems, Medical School, University of Warwick, Coventry CV4 7AL, UK.
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Carpéné C, Garcia-Vicente S, Serrano M, Marti L, Belles C, Royo M, Galitzky J, Zorzano A, Testar X. Insulin-mimetic compound hexaquis (benzylammonium) decavanadate is antilipolytic in human fat cells. World J Diabetes 2017; 8:143-153. [PMID: 28465791 PMCID: PMC5394734 DOI: 10.4239/wjd.v8.i4.143] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2016] [Revised: 11/14/2016] [Accepted: 01/18/2017] [Indexed: 02/05/2023] Open
Abstract
AIM To assess in rodent and human adipocytes the antilipolytic capacity of hexaquis(benzylammonium) decavanadate (B6V10), previously shown to exert antidiabetic effects in rodent models, such as lowering free fatty acids (FFA) and glucose circulating levels.
METHODS Adipose tissue (AT) samples were obtained after informed consent from overweight women undergoing plastic surgery. Comparison of the effects of B6V10 and reference antilipolytic agents (insulin, benzylamine, vanadate) on the lipolytic activity was performed on adipocytes freshly isolated from rat, mouse and human AT. Glycerol release was measured using colorimetric assay as an index of lipolytic activity. The influence of B6V10 and reference agents on glucose transport into human fat cells was determined using the radiolabelled 2-deoxyglucose uptake assay.
RESULTS In all the species studied, B6V10 exhibited a dose-dependent inhibition of adipocyte lipolysis when triglyceride breakdown was moderately enhanced by β-adrenergic receptor stimulation. B6V10 exerted on human adipocyte a maximal lipolysis inhibition of glycerol release that was stronger than that elicited by insulin. However, B6V10 did not inhibit basal and maximally stimulated lipolysis. When incubated at dose ≥ 10 μmol/L, B6V10 stimulated by twofold the glucose uptake in human fat cells, but - similarly to benzylamine - without reaching the maximal effect of insulin, while it reproduced one-half of the insulin-stimulation of lipogenesis in mouse fat cells.
CONCLUSION B6V10 exerts insulin-like actions in adipocytes, including lipolysis inhibition and glucose transport activation. B6V10 may be useful in limiting lipotoxicity related to obesity and insulin resistance.
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Mukherjee S, Chattopadhyay M, Bhattacharya S, Dasgupta S, Hussain S, Bharadwaj SK, Talukdar D, Usmani A, Pradhan BS, Majumdar SS, Chattopadhyay P, Mukhopadhyay S, Maity TK, Chaudhuri MK, Bhattacharya S. A Small Insulinomimetic Molecule Also Improves Insulin Sensitivity in Diabetic Mice. PLoS One 2017; 12:e0169809. [PMID: 28072841 PMCID: PMC5224995 DOI: 10.1371/journal.pone.0169809] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Accepted: 12/21/2016] [Indexed: 12/18/2022] Open
Abstract
Dramatic increase of diabetes over the globe is in tandem with the increase in insulin requirement. This is because destruction and dysfunction of pancreatic β-cells are of common occurrence in both Type1 diabetes and Type2 diabetes, and insulin injection becomes a compulsion. Because of several problems associated with insulin injection, orally active insulin mimetic compounds would be ideal substitute. Here we report a small molecule, a peroxyvanadate compound i.e. DmpzH[VO(O2)2(dmpz)], henceforth referred as dmp, which specifically binds to insulin receptor with considerable affinity (KD-1.17μM) thus activating insulin receptor tyrosine kinase and its downstream signaling molecules resulting increased uptake of [14C] 2 Deoxy-glucose. Oral administration of dmp to streptozotocin treated BALB/c mice lowers blood glucose level and markedly stimulates glucose and fatty acid uptake by skeletal muscle and adipose tissue respectively. In db/db mice, it greatly improves insulin sensitivity through excess expression of PPARγ and its target genes i.e. adiponectin, CD36 and aP2. Study on the underlying mechanism demonstrated that excess expression of Wnt3a decreased PPARγ whereas dmp suppression of Wnt3a gene increased PPARγ expression which subsequently augmented adiponectin. Increased production of adiponectin in db/db mice due to dmp effected lowering of circulatory TG and FFA levels, activates AMPK in skeletal muscle and this stimulates mitochondrial biogenesis and bioenergetics. Decrease of lipid load along with increased mitochondrial activity greatly improves energy homeostasis which has been found to be correlated with the increased insulin sensitivity. The results obtained with dmp, therefore, strongly indicate that dmp could be a potential candidate for insulin replacement therapy.
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Affiliation(s)
- Sandip Mukherjee
- Cellular and Molecular Endocrinology Laboratory, Centre for Advanced Studies in Zoology, School of Life Science, Visva-Bharati (A Central University), Santiniketan, West Bengal, India
| | - Mrittika Chattopadhyay
- Cellular and Molecular Endocrinology Laboratory, Centre for Advanced Studies in Zoology, School of Life Science, Visva-Bharati (A Central University), Santiniketan, West Bengal, India
| | | | - Suman Dasgupta
- Department of Molecular Biology and Biotechnology, Tezpur University, Assam, India
| | - Sahid Hussain
- Department of Chemical Sciences, Tezpur University, Assam, India
| | | | | | - Abul Usmani
- Division of Cellular Endocrinology, National Institute of Immunology, New Delhi, India
| | - Bhola S Pradhan
- Division of Cellular Endocrinology, National Institute of Immunology, New Delhi, India
| | - Subeer S Majumdar
- Division of Cellular Endocrinology, National Institute of Immunology, New Delhi, India
| | | | - Satinath Mukhopadhyay
- Department of Endocrinology & Metabolism, Institute of Post-Graduate Medical Education & Research-Seth Sukhlal Karnani Memorial (IPGME&R−SSKM) Hospital, Kolkata, West Bengal, India
| | | | - Mihir K. Chaudhuri
- Department of Chemical Sciences, Tezpur University, Assam, India
- * E-mail: (SB); (MKC)
| | - Samir Bhattacharya
- Cellular and Molecular Endocrinology Laboratory, Centre for Advanced Studies in Zoology, School of Life Science, Visva-Bharati (A Central University), Santiniketan, West Bengal, India
- * E-mail: (SB); (MKC)
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Synthesis, spectral characterization, DFT calculations, antimicrobial activity and molecular docking of 4-bromo-2-((2-hydroxy-5-methylphenylimino)methyl)phenol and its V(V) complex. Inorganica Chim Acta 2017. [DOI: 10.1016/j.ica.2016.10.018] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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25
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Subetta Enhances Sensitivity of Human Muscle Cells to Insulin. Bull Exp Biol Med 2015; 159:463-5. [DOI: 10.1007/s10517-015-2992-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2014] [Indexed: 11/25/2022]
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26
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Gorbunov EA, Nicoll J, Kachaeva EV, Tarasov SA, Epstein OI. Subetta increases phosphorylation of insulin receptor β-subunit alone and in the presence of insulin. Nutr Diabetes 2015; 5:e169. [PMID: 26148148 PMCID: PMC4521175 DOI: 10.1038/nutd.2015.20] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Revised: 05/19/2015] [Accepted: 05/31/2015] [Indexed: 11/13/2022] Open
Abstract
It has been previously shown that Subetta (a drug containing released-active forms of antibodies to the insulin receptor β-subunit and antibodies to endothelial nitric oxide synthase) stimulated insulin-induced adiponectin production by mature human adipocytes in the absence of insulin. Therefore, it was assumed that Subetta could activate the insulin receptor. To confirm this hypothesis, the capacity of Subetta to activate the insulin receptor in mature human adipocytes in the absence or presence of the insulin was investigated. Cells were incubated either with Subetta or with vehicle, or with basal medium for 3 days. Then, adipocytes were treated with water or insulin (100 nm) for 15 min. Following treatment, lysates were prepared and phosphorylation of insulin receptor β-subunits was analyzed by western blot analysis. It was shown that Subetta significantly increased (P<0.001) the ‘phosphorylated-insulin receptor β-subunit/total insulin receptor β-subunit' ratios in both the presence and the absence of insulin. These results support previously published data and indicate that Subetta could activate the insulin receptor through the effect on its β-subunits, whose conformational state is essential for insulin receptor activation. This action might serve as one of the primary mechanisms of the drug's antidiabetic effect.
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Affiliation(s)
- E A Gorbunov
- OOO 'NPF MATERIA MEDICA HOLDING', 47-1, Trifonovskaya street, Moscow 129272, Russian Federation
| | - J Nicoll
- Zen-Bio Inc., Research Triangle Park, NC, USA
| | - E V Kachaeva
- OOO 'NPF MATERIA MEDICA HOLDING', 47-1, Trifonovskaya street, Moscow 129272, Russian Federation
| | - S A Tarasov
- OOO 'NPF MATERIA MEDICA HOLDING', 47-1, Trifonovskaya street, Moscow 129272, Russian Federation
| | - O I Epstein
- OOO 'NPF MATERIA MEDICA HOLDING', 47-1, Trifonovskaya street, Moscow 129272, Russian Federation
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27
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Treviño S, Sánchez-Lara E, Sarmiento-Ortega VE, Sánchez-Lombardo I, Flores-Hernández JÁ, Pérez-Benítez A, Brambila-Colombres E, González-Vergara E. Hypoglycemic, lipid-lowering and metabolic regulation activities of metforminium decavanadate (H2Metf)3 [V10O28]·8H2O using hypercaloric-induced carbohydrate and lipid deregulation in Wistar rats as biological model. J Inorg Biochem 2015; 147:85-92. [PMID: 25920353 DOI: 10.1016/j.jinorgbio.2015.04.002] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2014] [Revised: 04/01/2015] [Accepted: 04/01/2015] [Indexed: 12/14/2022]
Abstract
Because of the increasing global spread of type 2 diabetes mellitus, there is a need to develop new antidiabetic agents. Recently we have synthesized new decavanadates using metformin as counterion. In particular, the compound containing three metforminium dications has been obtained in high yield and has been completely characterized. Biological studies using Wistar rats that have been fed with a high caloric diet inducing insulin resistance and metabolic syndrome were carried out. Results of the impact on key biochemical parameters mediated by metformin alone and the new compound are here presented. The metforminium decavanadate (H2Metf)3[V10O28]·8H2O, abbreviated as Metf-V10O28, was shown to have pharmacological potential as a hypoglycemic, lipid-lowering and metabolic regulator, since the resulting compound made of the two components with antidiabetic activities, reduces both dosage and time of administration (twice a week). Hence, due to the beneficial effects induced by the metforminium decavanadate we recommend to continue the exploration into the mechanism and toxicology of this new compound.
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Affiliation(s)
- Samuel Treviño
- Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, 14 Sur y Av. San Claudio, Col. San Manuel, CP 72570 Puebla, PUE, Mexico
| | - Eduardo Sánchez-Lara
- Centro de Química, ICUAP, Benemérita Universidad Autónoma de Puebla, 14 Sur y Av. San Claudio, Col. San Manuel, CP 72570 Puebla, PUE, Mexico
| | - Víctor Enrique Sarmiento-Ortega
- Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, 14 Sur y Av. San Claudio, Col. San Manuel, CP 72570 Puebla, PUE, Mexico
| | - Irma Sánchez-Lombardo
- Centro de Química, ICUAP, Benemérita Universidad Autónoma de Puebla, 14 Sur y Av. San Claudio, Col. San Manuel, CP 72570 Puebla, PUE, Mexico
| | - José Ángel Flores-Hernández
- Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, 14 Sur y Av. San Claudio, Col. San Manuel, CP 72570 Puebla, PUE, Mexico
| | - Aarón Pérez-Benítez
- Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, 14 Sur y Av. San Claudio, Col. San Manuel, CP 72570 Puebla, PUE, Mexico
| | - Eduardo Brambila-Colombres
- Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, 14 Sur y Av. San Claudio, Col. San Manuel, CP 72570 Puebla, PUE, Mexico
| | - Enrique González-Vergara
- Centro de Química, ICUAP, Benemérita Universidad Autónoma de Puebla, 14 Sur y Av. San Claudio, Col. San Manuel, CP 72570 Puebla, PUE, Mexico.
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28
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Levina A, McLeod AI, Pulte A, Aitken JB, Lay PA. Biotransformations of Antidiabetic Vanadium Prodrugs in Mammalian Cells and Cell Culture Media: A XANES Spectroscopic Study. Inorg Chem 2015; 54:6707-18. [PMID: 25906315 PMCID: PMC4511291 DOI: 10.1021/ic5028948] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
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The antidiabetic activities of vanadium(V)
and -(IV) prodrugs are determined by their ability to release active
species upon interactions with components of biological media. The
first X-ray absorption spectroscopic study of the reactivity of typical
vanadium (V) antidiabetics, vanadate ([VVO4]3–, A) and a vanadium(IV) bis(maltolato)
complex (B), with mammalian cell cultures has been performed
using HepG2 (human hepatoma), A549 (human lung carcinoma), and 3T3-L1
(mouse adipocytes and preadipocytes) cell lines, as well as the corresponding
cell culture media. X-ray absorption near-edge structure data were
analyzed using empirical correlations with a library of model vanadium(V),
-(IV), and -(III) complexes. Both A and B ([V] = 1.0 mM) gradually converged into similar mixtures of predominantly
five- and six-coordinate VV species (∼75% total
V) in a cell culture medium within 24 h at 310 K. Speciation of V
in intact HepG2 cells also changed with the incubation time (from
∼20% to ∼70% VIV of total V), but it was
largely independent of the prodrug used (A or B) or of the predominant V oxidation state in the medium. Subcellular
fractionation of A549 cells suggested that VV reduction
to VIV occurred predominantly in the cytoplasm, while accumulation
of VV in the nucleus was likely to have been facilitated
by noncovalent bonding to histone proteins. The nuclear VV is likely to modulate the transcription process and to be ultimately
related to cell death at high concentrations of V, which may be important
in anticancer activities. Mature 3T3-L1 adipocytes (unlike for preadipocytes)
showed a higher propensity to form VIV species, despite
the prevalence of VV in the medium. The distinct V biochemistry
in these cells is consistent with their crucial role in insulin-dependent
glucose and fat metabolism and may also point to an endogenous role
of V in adipocytes. The first detailed
speciation study of typical antidiabetic vanadium(V/IV) complexes
in mammalian cell culture systems showed that the complexes decomposed
rapidly in cell culture media and were further metabolized by the
cells, which included interconversions of VV and VIV species.
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Affiliation(s)
- Aviva Levina
- School of Chemistry, The University of Sydney, Sydney, New South Wales 2006, Australia
| | - Andrew I McLeod
- School of Chemistry, The University of Sydney, Sydney, New South Wales 2006, Australia
| | - Anna Pulte
- School of Chemistry, The University of Sydney, Sydney, New South Wales 2006, Australia
| | - Jade B Aitken
- School of Chemistry, The University of Sydney, Sydney, New South Wales 2006, Australia
| | - Peter A Lay
- School of Chemistry, The University of Sydney, Sydney, New South Wales 2006, Australia
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29
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Qiang G, Xue S, Yang JJ, Du G, Pang X, Li X, Goswami D, Griffin PR, Ortlund EA, Chan CB, Ye K. Identification of a small molecular insulin receptor agonist with potent antidiabetes activity. Diabetes 2014; 63:1394-409. [PMID: 24651808 PMCID: PMC3964510 DOI: 10.2337/db13-0334] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Insulin replacement therapy is a widely adopted treatment for all patients with type 1 diabetes and some with type 2 diabetes. However, injection of insulin has suffered from problems such as tissue irritation, abscesses, discomfort, and inconvenience. The use of orally bioactive insulin mimetics thus represents an ideal treatment alternative. Here we show that a chaetochromin derivative (4548-G05) acts as a new nonpeptidyl insulin mimetic. 4548-G05 selectively activates an insulin receptor (IR) but not insulin-like growth factor receptor-I or other receptor tyrosine kinases. Through binding to the extracellular domain of the IR, 4548-G05 induces activation of the receptor and initiates the downstream Akt and extracellular signal-related kinase pathways to trigger glucose uptake in C2C12 myotubes. Moreover, it displays a potent blood glucose-lowering effect when administrated orally in normal, type 1 diabetic, and type 2 diabetic mice models. Therefore, 4548-G05 may represent a novel pharmacological agent for antidiabetes drug development.
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Affiliation(s)
- Guifen Qiang
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA
| | - Shenghui Xue
- Departments of Chemistry and Biology, Center for Diagnostics and Therapeutics (CDT), Georgia State University, Atlanta, GA
| | - Jenny J. Yang
- Departments of Chemistry and Biology, Center for Diagnostics and Therapeutics (CDT), Georgia State University, Atlanta, GA
| | - Guanhua Du
- National Center for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaobin Pang
- National Center for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Institute of Pharmacy, Henan University, Kaifeng, China
| | - Xiaoting Li
- National Center for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Institute of Pharmacy, Henan University, Kaifeng, China
| | - Devrishi Goswami
- Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL
| | - Patrick R. Griffin
- Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL
| | - Eric A. Ortlund
- Department of Biochemistry, Emory University School of Medicine, Atlanta, GA
| | - Chi Bun Chan
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA
- Corresponding author: Chi Bun Chan, , or Keqiang Ye,
| | - Keqiang Ye
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA
- Corresponding author: Chi Bun Chan, , or Keqiang Ye,
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30
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Lacroix IME, Li-Chan ECY. Overview of food products and dietary constituents with antidiabetic properties and their putative mechanisms of action: a natural approach to complement pharmacotherapy in the management of diabetes. Mol Nutr Food Res 2013; 58:61-78. [PMID: 23943383 DOI: 10.1002/mnfr.201300223] [Citation(s) in RCA: 76] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2013] [Revised: 06/10/2013] [Accepted: 06/13/2013] [Indexed: 01/05/2023]
Abstract
Diabetes is one of the fastest growing chronic, noncommunicable diseases worldwide. Currently, 11 major classes of pharmacotherapy are available for the management of this metabolic disorder. However, the usage of these drugs is often associated with undesirable side effects, including weight gain and hypoglycemia. There is thus a need for new, safe and effective treatment strategies. Diet is known to play a major role in the prevention and management of diabetes. Numerous studies have reported the putative association of the consumption of specific food products, or their constituents, with the incidence of diabetes, and mounting evidence now suggests that some dietary factors can improve glycemic regulation. Foods and dietary constituents, similar to synthetic drugs, have been shown to modulate hormones, enzymes, and organ systems involved in carbohydrate metabolism. The present article reviews the major classes and modes of action of antidiabetic drugs, and examines the evidence on food products and dietary factors with antidiabetic properties as well as their plausible mechanisms of action. The findings suggest potential use of dietary constituents as a complementary approach to pharmacotherapy in the prevention and/or management of diabetes, but further research is necessary to identify the active components and evaluate their efficacy and safety.
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Affiliation(s)
- Isabelle M E Lacroix
- Faculty of Land & Food Systems, Food Nutrition & Health Program, The University of British Columbia, Vancouver, BC, Canada
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31
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Chatkon A, Chatterjee PB, Sedgwick MA, Haller KJ, Crans DC. Counterion Affects Interaction with Interfaces: The Antidiabetic Drugs Metformin and Decavanadate. Eur J Inorg Chem 2013. [DOI: 10.1002/ejic.201201345] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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32
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Krol S, Ellis-Behnke R, Marchetti P. Nanomedicine for treatment of diabetes in an aging population: state-of-the-art and future developments. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2012; 8 Suppl 1:S69-76. [PMID: 22640905 DOI: 10.1016/j.nano.2012.05.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2011] [Revised: 12/01/2011] [Accepted: 12/03/2011] [Indexed: 01/05/2023]
Abstract
Nowadays diabetes, especially type 2 diabetes (which is strongly related to the Western diet and life-style), has developed worldwide into an epidemic disease. Nanomedicine aims to provide novel tools for diagnosis, therapy and point-of-care management of patients. Several nanotechnological approaches were developed to improve life quality for patients with insulin-dependent diabetes. They facilitate blood glucose management by non-invasive glucose measurement as well as insulin administration mainly by delivering the fragile protein as protected and targeted formulation via nasal or oral route. In the present review the oral or nasal insulin delivery by polymeric nanoparticles is discussed with focus on physiological change either related to the disease, diabetes or age-related metabolic variations influencing insulin release and bioavailability. One critical point is that new generations of targeted nanoparticle based drugs are developed and optimized for certain metabolic conditions. These conditions may change with age or disease. The influence of age-related factors such as immaturity in very young age, metabolic and physiologic changes in old age or insufficient animal models are still under-investigated not only in nanomedicine but also generally in pharmacology. Summarizing it can be noted that the bioavailability of insulin administered via routes others than subcutaneously is comparably low (max. 60%). Moreover factors like changed gut permeability as described for diabetes type 1 or other metabolic peculiarities such as insulin resistance in case of type 2 diabetes also play a role in affecting the development of novel nanoparticulated drug preparations and can be responsible for unsuccessful translation of promising animal results into human therapy. In future insulin nanoparticle development for diabetes must consider not only requirements imposed by the drug but also metabolic changes inflicted by disease or by age. Moreover new approaches are required for prevention of the disease.
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Affiliation(s)
- Silke Krol
- Fondazione IRCCS Istituto Neurologico Carlo Besta, IFOM-IEO-Campus, via Adamello 16, 201394 Milan, Italy.
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33
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Krol S, Ellis-Behnke R, Marchetti P. Nanomedicine for treatment of diabetes in an aging population: state-of-the-art and future developments. Maturitas 2011; 73:61-7. [PMID: 22209199 DOI: 10.1016/j.maturitas.2011.12.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2011] [Revised: 12/01/2011] [Accepted: 12/03/2011] [Indexed: 01/08/2023]
Abstract
Nowadays diabetes, especially type 2 diabetes (which is strongly related to the Western diet and life-style), has developed worldwide into an epidemic disease. Nanomedicine aims to provide novel tools for diagnosis, therapy and point-of-care management of patients. Several nanotechnological approaches were developed to improve life quality for patients with insulin-dependent diabetes. They facilitate blood glucose management by non-invasive glucose measurement as well as insulin administration mainly by delivering the fragile protein as protected and targeted formulation via nasal or oral route. In the present review the oral or nasal insulin delivery by polymeric nanoparticles is discussed with focus on physiological change either related to the disease, diabetes or age-related metabolic variations influencing insulin release and bioavailability. One critical point is that new generations of targeted nanoparticle based drugs are developed and optimized for certain metabolic conditions. These conditions may change with age or disease. The influence of age-related factors such as immaturity in very young age, metabolic and physiologic changes in old age or insufficient animal models are still under-investigated not only in nanomedicine but also generally in pharmacology. Summarizing it can be noted that the bioavailability of insulin administered via routes others than subcutaneously is comparably low (max. 60%). Moreover factors like changed gut permeability as described for diabetes type 1 or other metabolic peculiarities such as insulin resistance in case of type 2 diabetes also play a role in affecting the development of novel nanoparticulated drug preparations and can be responsible for unsuccessful translation of promising animal results into human therapy. In future insulin nanoparticle development for diabetes must consider not only requirements imposed by the drug but also metabolic changes inflicted by disease or by age. Moreover new approaches are required for prevention of the disease.
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Affiliation(s)
- Silke Krol
- Fondazione IRCCS Istituto Neurologico Carlo Besta, IFOM-IEO-Campus, Milan, Italy.
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34
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Abstract
The current status and likely future directions of complexes of V(V/IV), Cr(III), Mo(VI), W(VI), Zn(II), Cu(II), and Mn(III) as potential oral drugs against type 2 diabetes are reviewed. We propose a unified model of extra- and intracellular mechanisms of anti-diabetic efficacies of V(V/IV), Mo(VI), W(VI), and Cr(III), centred on high-oxidation-state oxido/peroxido species that inhibit protein tyrosine phosphatases (PTPs) involved in insulin signalling. The postulated oxidative mechanism of anti-diabetic activity of Cr(III) via carcinogenic Cr(VI/V) (which adds to safety concerns) is consistent with recent clinical trials on Cr(III) picolinate, where activity was apparent only in patients with poorly controlled diabetes (high oxidative stress), and the correlation between the anti-diabetic activities and ease of oxidation of Cr(III) supplements and their metabolites in vivo. Zn(II) and Cu(II) anti-diabetics act via different mechanisms and are unlikely to be used as specific anti-diabetics due to their diverse and unpredictable biological activities. Hence, future research directions are likely to centre on enhancing the bioavailability and selectivity of V(V/IV), Mo(VI), or W(VI) drugs. The strategy of potentiating circulating insulin with metal ions has distinct therapeutic advantages over interventions that stimulate the release of more insulin, or use insulin mimetics, because of many adverse side-effects of increased levels of insulin, including increased risks of cancer and cardiovascular diseases.
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Affiliation(s)
- Aviva Levina
- School of Chemistry, The University of Sydney, NSW, Australia
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35
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Abstract
The increasing prevalence, variable pathogenesis, progressive natural history, and complications of type 2 diabetes emphasise the urgent need for new treatment strategies. Longacting (eg, once weekly) agonists of the glucagon-like-peptide-1 receptor are advanced in development, and they improve prandial insulin secretion, reduce excess glucagon production, and promote satiety. Trials of inhibitors of dipeptidyl peptidase 4, which enhance the effect of endogenous incretin hormones, are also nearing completion. Novel approaches to glycaemic regulation include use of inhibitors of the sodium-glucose cotransporter 2, which increase renal glucose elimination, and inhibitors of 11β-hydroxysteroid dehydrogenase 1, which reduce the glucocorticoid effects in liver and fat. Insulin-releasing glucokinase activators and pancreatic-G-protein-coupled fatty-acid-receptor agonists, glucagon-receptor antagonists, and metabolic inhibitors of hepatic glucose output are being assessed. Early proof of principle has been shown for compounds that enhance and partly mimic insulin action and replicate some effects of bariatric surgery.
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Affiliation(s)
- Abd A Tahrani
- Centre of Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham, UK
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36
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Wiernsperger N, Rapin J. Trace elements in glucometabolic disorders: an update. Diabetol Metab Syndr 2010; 2:70. [PMID: 21167072 PMCID: PMC3023745 DOI: 10.1186/1758-5996-2-70] [Citation(s) in RCA: 87] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2010] [Accepted: 12/19/2010] [Indexed: 12/17/2022] Open
Abstract
Many trace elements, among which metals, are indispensable for proper functioning of a myriad of biochemical reactions, more particularly as enzyme cofactors. This is particularly true for the vast set of processes involved in regulation of glucose homeostasis, being it in glucose metabolism itself or in hormonal control, especially insulin. The role and importance of trace elements such as chromium, zinc, selenium, lithium and vanadium are much less evident and subjected to chronic debate. This review updates our actual knowledge concerning these five trace elements. A careful survey of the literature shows that while theoretical postulates from some key roles of these elements had led to real hopes for therapy of insulin resistance and diabetes, the limited experience based on available data indicates that beneficial effects and use of most of them are subjected to caution, given the narrow window between safe and unsafe doses. Clear therapeutic benefit in these pathologies is presently doubtful but some data indicate that these metals may have a clinical interest in patients presenting deficiencies in individual metal levels. The same holds true for an association of some trace elements such as chromium or zinc with oral antidiabetics. However, this area is essentially unexplored in adequate clinical trials, which are worth being performed.
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Affiliation(s)
| | - JeanRobert Rapin
- Faculté de Médecine/Pharmacie, Université de Bourgogne, 3 Bld jeanne d'Arc, F-21000 Dijon (France
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37
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Jarrell JD, Dolly B, Morgan JR. Rapid screening, in vitro study of metal oxide and polymer hybrids as delivery coatings for improved soft-tissue integration of implants. J Biomed Mater Res A 2010; 92:1094-104. [PMID: 19301265 DOI: 10.1002/jbm.a.32435] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Metal-organic chemistry allows for molecular mixing and creation of a range of submicron phase-separated structures from normally brittle metal oxides and flexible polymers with improved bioactivity and delivery properties. In this study, we used a high throughput platform to investigate the influence of organic metal oxide doping of polydimethylsiloxane (PDMS) coatings on cellular bioactivity and controlled release of vanadium compared with titanium oxide coatings without additional PDMS. Metal-organic-derived titanium and or vanadium was doped into PDMS and used to form a coating on the bottom of cell culture microplates in the absence of added water, acids, or bases. These hybrid coatings were rapidly screened to establish how titanium and vanadium concentration influences cell proliferation, adhesion, and morphology. We demonstrate that titanium doping of PDMS can be used to improve cell proliferation and adhesion, and that vanadium doping caused a biphasic dose response in proliferation. A 28-day vanadium and titanium elution study indicated that titanium was not released, but the presence of PDMS in coatings increased delivery rates of vanadium compared with titania coatings without polymer. Hybrid coatings of titanium-doped polymers have potential for improving wound healing dynamics, soft-tissue integration of medical implants, and use as controlled delivery vehicles.
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Affiliation(s)
- John D Jarrell
- Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, Rhode Island, USA.
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38
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Truflandier LA, Boucher F, Payen C, Hajjar R, Millot Y, Bonhomme C, Steunou N. DFT-NMR Investigation and 51V 3QMAS Experiments for Probing Surface OH Ligands and the Hydrogen-Bond Network in a Polyoxovanadate Cluster: The Case of Cs4[H2V10O28]·4H2O. J Am Chem Soc 2010; 132:4653-68. [DOI: 10.1021/ja908973y] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Affiliation(s)
- Lionel A. Truflandier
- Institut des Matériaux Jean Rouxel (IMN), Université de Nantes, UMR CNRS 6502, 2 rue de la Houssinière, BP 32229, 44340 Nantes Cedex 3, France, Laboratoire des Systèmes Interfaciaux à l’Echelle Nanométrique (SIEN), UMR CNRS 7142, UPMC Univ Paris 06, 4 place Jussieu, 75252 Paris Cedex 05, France, and Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), UMR CNRS 7574, UPMC Univ Paris 06, Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France
| | - Florent Boucher
- Institut des Matériaux Jean Rouxel (IMN), Université de Nantes, UMR CNRS 6502, 2 rue de la Houssinière, BP 32229, 44340 Nantes Cedex 3, France, Laboratoire des Systèmes Interfaciaux à l’Echelle Nanométrique (SIEN), UMR CNRS 7142, UPMC Univ Paris 06, 4 place Jussieu, 75252 Paris Cedex 05, France, and Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), UMR CNRS 7574, UPMC Univ Paris 06, Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France
| | - Christophe Payen
- Institut des Matériaux Jean Rouxel (IMN), Université de Nantes, UMR CNRS 6502, 2 rue de la Houssinière, BP 32229, 44340 Nantes Cedex 3, France, Laboratoire des Systèmes Interfaciaux à l’Echelle Nanométrique (SIEN), UMR CNRS 7142, UPMC Univ Paris 06, 4 place Jussieu, 75252 Paris Cedex 05, France, and Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), UMR CNRS 7574, UPMC Univ Paris 06, Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France
| | - Redouane Hajjar
- Institut des Matériaux Jean Rouxel (IMN), Université de Nantes, UMR CNRS 6502, 2 rue de la Houssinière, BP 32229, 44340 Nantes Cedex 3, France, Laboratoire des Systèmes Interfaciaux à l’Echelle Nanométrique (SIEN), UMR CNRS 7142, UPMC Univ Paris 06, 4 place Jussieu, 75252 Paris Cedex 05, France, and Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), UMR CNRS 7574, UPMC Univ Paris 06, Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France
| | - Yannick Millot
- Institut des Matériaux Jean Rouxel (IMN), Université de Nantes, UMR CNRS 6502, 2 rue de la Houssinière, BP 32229, 44340 Nantes Cedex 3, France, Laboratoire des Systèmes Interfaciaux à l’Echelle Nanométrique (SIEN), UMR CNRS 7142, UPMC Univ Paris 06, 4 place Jussieu, 75252 Paris Cedex 05, France, and Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), UMR CNRS 7574, UPMC Univ Paris 06, Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France
| | - Christian Bonhomme
- Institut des Matériaux Jean Rouxel (IMN), Université de Nantes, UMR CNRS 6502, 2 rue de la Houssinière, BP 32229, 44340 Nantes Cedex 3, France, Laboratoire des Systèmes Interfaciaux à l’Echelle Nanométrique (SIEN), UMR CNRS 7142, UPMC Univ Paris 06, 4 place Jussieu, 75252 Paris Cedex 05, France, and Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), UMR CNRS 7574, UPMC Univ Paris 06, Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France
| | - Nathalie Steunou
- Institut des Matériaux Jean Rouxel (IMN), Université de Nantes, UMR CNRS 6502, 2 rue de la Houssinière, BP 32229, 44340 Nantes Cedex 3, France, Laboratoire des Systèmes Interfaciaux à l’Echelle Nanométrique (SIEN), UMR CNRS 7142, UPMC Univ Paris 06, 4 place Jussieu, 75252 Paris Cedex 05, France, and Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), UMR CNRS 7574, UPMC Univ Paris 06, Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France
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Bonaiuto E, Lunelli M, Scarpa M, Vettor R, Milan G, Di Paolo ML. A structure-activity study to identify novel and efficient substrates of the human semicarbazide-sensitive amine oxidase/VAP-1 enzyme. Biochimie 2010; 92:858-68. [PMID: 20298739 DOI: 10.1016/j.biochi.2010.03.006] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2010] [Accepted: 03/10/2010] [Indexed: 01/09/2023]
Abstract
Kinetic studies were performed with various alkanamines as "substrate probes" of the properties of the active site of the human semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1). We found that the enzyme-substrate recognition step is mainly controlled by apolar interactions and that a "good" substrate has a molecular structure containing a long aliphatic chain and a second positive charge at a distance greater than 12 A from the reactive amino group. In this context, we identified a novel substrate for the human SSAO/VAP-1, 1,12-diaminododecane (DIADO), which is characterised by the highest catalytic efficiency reported to date in comparison to the prototypic substrate benzylamine. Computational docking studies revealed the structural basis of this behaviour, highlighting the key role played by Lys393 in hindering substrate docking. Maximum SSAO/VAP-1 activity is reached at relatively low concentrations of DIADO (10-30 microM), and, in these conditions, it has good selectivity: it is a good substrate of SSAO/VAP-1 but not of human adipocyte monoamine oxidases or pig kidney diamine oxidase. From these findings, it appears that DIADO can be used as a new substrate for human SSAO/VAP-1 to elicit glucose transport into adipocytes, and may consequently have potential pharmacological applications in the design of anti-diabetic agents.
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Affiliation(s)
- Emanuela Bonaiuto
- Department of Biological Chemistry, University of Padova, Via G. Colombo, 3, 35131 Padova, Italy
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Chronic benzylamine administration in the drinking water improves glucose tolerance, reduces body weight gain and circulating cholesterol in high-fat diet-fed mice. Pharmacol Res 2010; 61:355-63. [PMID: 20045461 DOI: 10.1016/j.phrs.2009.12.014] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2009] [Revised: 12/23/2009] [Accepted: 12/23/2009] [Indexed: 12/27/2022]
Abstract
Benzylamine is found in Moringa oleifera, a plant used to treat diabetes in traditional medicine. In mammals, benzylamine is metabolized by semicarbazide-sensitive amine oxidase (SSAO) to benzaldehyde and hydrogen peroxide. This latter product has insulin-mimicking action, and is involved in the effects of benzylamine on human adipocytes: stimulation of glucose transport and inhibition of lipolysis. This study examined whether chronic, oral administration of benzylamine could improve glucose tolerance and the circulating lipid profile without increasing oxidative stress in overweight and pre-diabetic mice. The benzylamine diffusion across the intestine was verified using everted gut sacs. Then, glucose handling and metabolic markers were measured in mice rendered insulin-resistant when fed a high-fat diet (HFD) and receiving or not benzylamine in their drinking water (3600micromol/(kgday)) for 17 weeks. HFD-benzylamine mice showed lower body weight gain, fasting blood glucose, total plasma cholesterol and hyperglycaemic response to glucose load when compared to HFD control. In adipocytes, insulin-induced activation of glucose transport and inhibition of lipolysis remained unchanged. In aorta, benzylamine treatment partially restored the nitrite levels that were reduced by HFD. In liver, lipid peroxidation markers were reduced. Resistin and uric acid, surrogate plasma markers of metabolic syndrome, were decreased. In spite of the putative deleterious nature of the hydrogen peroxide generated during amine oxidation, and in agreement with its in vitro insulin-like actions found on adipocytes, the SSAO-substrate benzylamine could be considered as a potential oral agent to treat metabolic syndrome.
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Pereira MJ, Carvalho E, Eriksson JW, Crans DC, Aureliano M. Effects of decavanadate and insulin enhancing vanadium compounds on glucose uptake in isolated rat adipocytes. J Inorg Biochem 2009; 103:1687-1692. [PMID: 19850351 DOI: 10.1016/j.jinorgbio.2009.09.015] [Citation(s) in RCA: 75] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2009] [Revised: 09/17/2009] [Accepted: 09/21/2009] [Indexed: 02/07/2023]
Abstract
The effects of different vanadium compounds namely pyridine-2,6-dicarboxylatedioxovanadium(V) (V5-dipic), bis(maltolato) oxovanadium(IV) (BMOV) and amavadine, and oligovanadates namely metavanadate and decavanadate were analysed on basal and insulin stimulated glucose uptake in rat adipocytes. Decavanadate (50 microM), manifest a higher increases (6-fold) on glucose uptake compared with basal, followed by BMOV (1 mM) and metavanadate (1 mM) solutions (3-fold) whereas V5 dipic and amavadine had no effect. Decavanadate (100 microM) also shows the highest insulin like activity when compared with the others compounds studied. In the presence of insulin (10 nM), only decavanadate increases (50%) the glucose uptake when compared with insulin stimulated glucose uptake whereas BMOV and metavanadate, had no effect and V5 dipic and amavadine prevent the stimulation to about half of the basal value. Decavanadate is also able to reduce or eradicate the suppressor effect caused by dexamethasone on glucose uptake at the level of the adipocytes. Altogether, vanadium compounds and oligovanadates with several structures and coordination spheres reveal different effects on glucose uptake in rat primary adipocytes.
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Affiliation(s)
- Maria João Pereira
- CCMAR and FCT, University of Algarve, Campus das Gambelas, 8005-139 Faro, Portugal
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Abstract
Currently, efforts have been directed towards using decavanadate as a tool for the understanding of several biochemical processes such as muscle contraction, calcium homeostasis, in vivo changes of oxidative stress markers, mitochondrial oxygen consumption, mitochondrial membrane depolarization, actin polymerization and glucose uptake, among others. In addition, studies have been conducted in order to make vanadium available and safe for clinical use, for instance with decavanadate compounds that present interesting pharmacological properties, eventually useful for the treatment of diabetes. Here, recent contributions of decavanadate to the effects of vanadium in biological systems, not only in vitro, but also in vivo, are analysed.
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Affiliation(s)
- Manuel Aureliano
- Faculty of Sciences and Technology, University of Algarve, Portugal.
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Bošnjaković-Pavlović N, Spasojević-de Biré A, Tomaz I, Bouhmaida N, Avecilla F, Mioč UB, Pessoa JC, Ghermani NE. Electronic Properties of a Cytosine Decavanadate: Toward a Better Understanding of Chemical and Biological Properties of Decavanadates. Inorg Chem 2009; 48:9742-53. [DOI: 10.1021/ic9008575] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Nada Bošnjaković-Pavlović
- Laboratoire Structures, Propriétés et Modélisation des Solides (SPMS), UMR CNRS 8580, Ecole Centrale Paris, Grande Voie des Vignes, 92295 Châtenay-Malabry, France
- Faculty of Physical Chemistry, University of Belgrade, P.O. Box 47, 11158 Belgrade, PAC 105305, Serbia
| | - Anne Spasojević-de Biré
- Laboratoire Structures, Propriétés et Modélisation des Solides (SPMS), UMR CNRS 8580, Ecole Centrale Paris, Grande Voie des Vignes, 92295 Châtenay-Malabry, France
| | - Isabel Tomaz
- Centro de Quimica Estrutural, Instituto Superior Tecnico, TU Lisbon, Av. Rovisco Pais, 1049-001 Lisboa, Portugal
| | - Nouzha Bouhmaida
- Laboratoire des Sciences des Matériaux (LSM) Université Cadi Ayyad, Faculté des Sciences Semlalia, Boulevard Prince Moulay Abdallah, BP 2390, 40000 Marrakech, Morocco
| | - Fernando Avecilla
- Departamento de Química Fundamental, Facultad de Ciencias, Universidade da Coruña, Campus da Zapateira s/n, 15071 A Coruña, Spain
| | - Ubavka B. Mioč
- Faculty of Physical Chemistry, University of Belgrade, P.O. Box 47, 11158 Belgrade, PAC 105305, Serbia
| | - João Costa Pessoa
- Centro de Quimica Estrutural, Instituto Superior Tecnico, TU Lisbon, Av. Rovisco Pais, 1049-001 Lisboa, Portugal
| | - Nour Eddine Ghermani
- Laboratoire Structures, Propriétés et Modélisation des Solides (SPMS), UMR CNRS 8580, Ecole Centrale Paris, Grande Voie des Vignes, 92295 Châtenay-Malabry, France
- Laboratoire de Physique Pharmaceutique, UMR CNRS 8612, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France
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Yraola F, Zorzano A, Albericio F, Royo M. Structure-activity relationships of SSAO/VAP-1 arylalkylamine-based substrates. ChemMedChem 2009; 4:495-503. [PMID: 19266512 DOI: 10.1002/cmdc.200800393] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1) substrates show insulin-mimetic effects and are therefore potentially valuable molecules for the treatment of diabetes mellitus. Herein we review several structural and electronic aspects of SSAO arylalkylamine-based substrates. Two main modifications directly affect amine oxidase (AO) activity: 1) variation in ring substitution modulates the biological activity of the arylalkylamine ligand by converting a substrate into a substrate-like inhibitor, and 2) variation in the number of methylene units between the aromatic ring and the ammonium groups of the arylalkylamine substrates dramatically alters the oxidation rate between species. Furthermore, we review relevant information about mammalian SSAO/VAP-1 substrate selectivity and specificity over monoamine oxidases (MAOs).
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Jarrell JD, Dolly B, Morgan JR. Controlled release of vanadium from titanium oxide coatings for improved integration of soft tissue implants. J Biomed Mater Res A 2009; 90:272-81. [DOI: 10.1002/jbm.a.32093] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Zorzano A, Palacín M, Marti L, García-Vicente S. Arylalkylamine vanadium salts as new anti-diabetic compounds. J Inorg Biochem 2009; 103:559-66. [PMID: 19246098 DOI: 10.1016/j.jinorgbio.2009.01.015] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2008] [Revised: 12/24/2008] [Accepted: 01/16/2009] [Indexed: 01/27/2023]
Abstract
Vanadium compounds show insulin-like effects in vivo and in vitro. Several clinical studies have shown the efficacy of vanadium compounds in type 2 diabetic subjects. However, a major concern is safety, which calls for the development of more potent vanadium compounds. For that reason different laboratories develop strategies to decrease the therapeutic dose of vanadate. One of these strategies use substrates of semicarbazide-sensitive amine oxidase (SSAO)/vascular adhesion protein-1 (VAP-1), a bifunctional protein with amine oxidase activity and adhesive properties implicated in lymphocyte homing at inflammation sites. Substrates of SSAO combined with low concentrations of vanadate strongly stimulate glucose transport and GLUT4 glucose transporter recruitment to the plasma membrane in 3T3-L1 adipocytes and in rat adipocytes. This combination also shows anti-diabetic effects in various animal models of type 1 and type 2 diabetes. Benzylamine/vanadate administration generates peroxovanadium locally in pancreatic islets, which stimulates insulin secretion, and also produces peroxovanadium in adipose tissue, thereby activating glucose metabolism in adipocytes and in neighboring muscle. This opens up the possibility of using the SSAO/VAP-1 activity as a local generator of protein tyrosine phosphatase inhibitors in anti-diabetic therapy. More recently a novel class of arylalkylaminevanadium salts have shown potent insulin-mimetic effects downstream of the insulin receptor. Administration of these compounds lowers glycemia and normalizes the plasma lipid profile in type 1 and type 2 models of diabetes. The combination of different approaches to decrease vanadium doses, among them chelating agents and SSAO substrates, should permit to develop safe and efficient vanadium based agents safe for diabetes treatment.
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Affiliation(s)
- Antonio Zorzano
- Institute for Research in Biomedicine (IRB Barcelona), C/Baldiri Reixac 10, Barcelona, Spain.
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Mohler ML, He Y, Wu Z, Hwang DJ, Miller DD. Recent and emerging anti-diabetes targets. Med Res Rev 2009; 29:125-95. [DOI: 10.1002/med.20142] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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Impairment of ascorbic acid’s anti-oxidant properties in confined media: Inter and intramolecular reactions with air and vanadate at acidic pH. J Inorg Biochem 2008; 102:1334-47. [DOI: 10.1016/j.jinorgbio.2008.01.015] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2007] [Revised: 01/04/2008] [Accepted: 01/10/2008] [Indexed: 11/22/2022]
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Iffiú-Soltész Z, Prévot D, Grès S, Bour S, Szökö E, Knauf C, Burcelin R, Fernández-Quintela A, Lomba A, Milagro FI, Carpéné C. Influence of acute and chronic administration of benzylamine on glucose tolerance in diabetic and obese mice fed on very high-fat diet. J Physiol Biochem 2007; 63:305-15. [DOI: 10.1007/bf03165762] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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50
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Wei D, Li M, Ding W. Effect of vanadate on gene expression of the insulin signaling pathway in skeletal muscle of streptozotocin-induced diabetic rats. J Biol Inorg Chem 2007; 12:1265-73. [PMID: 17874149 DOI: 10.1007/s00775-007-0294-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2007] [Accepted: 08/20/2007] [Indexed: 11/30/2022]
Abstract
An insulin signaling pathway microarray was used to evaluate the gene expression profiling of the insulin signaling pathway in the skeletal muscle of streptozotocin-induced diabetic, NaVO(3)-treated diabetic and insulin-treated diabetic rats for the investigation of the effect of vanadium and insulin on the insulin signaling pathway. Of 96 genes surveyed, transcriptional patterns of 19 genes (20%) showed alterations in diabetic rats compared with controls. Although most of these changed gene expressions were improved after treatment with NaVO(3) (14, 74%) and insulin (16, 84%), NaVO(3) and insulin treatment resulted in the alteration of 20 and 12 additional gene transcripts compared no treatment. We found that both NaVO(3) and insulin treatment achieved a desirable glucose level and most of the alterative gene transcripts in diabetic rats were normalized with NaVO(3) and insulin treatment. Comparison of the gene expression profiling indicates that there is a significant difference between the NaVO(3)-treated group and the insulin-treated group. The present study demonstrated for the first time that several candidate genes of the insulin signaling pathway are involved in the effect of vanadium treatment on hyperglycemia. This study opens the way for more focused investigations that may identify the genes responsible for diabetes and vanadium treatment in the global insulin signaling pathway.
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Affiliation(s)
- Dan Wei
- Department of Biology, Graduate University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, People's Republic of China
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