|
1
|
Bellomo C, Furone F, Rotondo R, Ciscognetti I, Carpinelli M, Nicoletti M, D’Aniello G, Sepe L, Barone MV, Nanayakkara M. Role of Protein Tyrosine Phosphatases in Inflammatory Bowel Disease, Celiac Disease and Diabetes: Focus on the Intestinal Mucosa. Cells 2024; 13:1981. [PMID: 39682729 PMCID: PMC11640621 DOI: 10.3390/cells13231981] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 11/19/2024] [Accepted: 11/25/2024] [Indexed: 12/18/2024] Open
Abstract
Protein tyrosine phosphatases (PTPs) are a family of enzymes essential for numerous cellular processes, such as cell growth, inflammation, differentiation, immune-mediated responses and oncogenic transformation. The aim of this review is to review the literature concerning the role of several PTPs-PTPN22, PTPN2, PTPN6, PTPN11, PTPσ, DUSP2, DUSP6 and PTPRK-at the level of the intestinal mucosa in inflammatory bowel disease (IBD), celiac disease (CeD) and type 1 diabetes (T1D) in both in vitro and in vivo models. The results revealed shared features, at the level of the intestinal mucosa, between these diseases characterized by alterations of different biological processes, such as proliferation, autoimmunity, cell death, autophagy and inflammation. PTPs are now actively studied to develop new drugs. Also considering the availability of organoids as models to test new drugs in personalized ways, it is very likely that soon these proteins will be the targets of useful drugs.
Collapse
Affiliation(s)
- Claudia Bellomo
- Department of Translational Medical Science, Section of Pediatrics, University Federico II, Via S. Pansini 5, 80131 Naples, Italy; (C.B.); (F.F.); (I.C.); (M.C.); (M.N.)
| | - Francesca Furone
- Department of Translational Medical Science, Section of Pediatrics, University Federico II, Via S. Pansini 5, 80131 Naples, Italy; (C.B.); (F.F.); (I.C.); (M.C.); (M.N.)
| | - Roberta Rotondo
- Department of Medicine and Surgery, University of Parma, 43121 Parma, Italy;
| | - Ilaria Ciscognetti
- Department of Translational Medical Science, Section of Pediatrics, University Federico II, Via S. Pansini 5, 80131 Naples, Italy; (C.B.); (F.F.); (I.C.); (M.C.); (M.N.)
| | - Martina Carpinelli
- Department of Translational Medical Science, Section of Pediatrics, University Federico II, Via S. Pansini 5, 80131 Naples, Italy; (C.B.); (F.F.); (I.C.); (M.C.); (M.N.)
| | - Martina Nicoletti
- Department of Translational Medical Science, Section of Pediatrics, University Federico II, Via S. Pansini 5, 80131 Naples, Italy; (C.B.); (F.F.); (I.C.); (M.C.); (M.N.)
| | - Genoveffa D’Aniello
- ELFID (European Laboratory for the Investigation of Food-Induced Diseases), University Federico II, Via S. Pansini 5, 80131 Naples, Italy;
| | - Leandra Sepe
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy;
| | - Maria Vittoria Barone
- Department of Translational Medical Science, Section of Pediatrics, University Federico II, Via S. Pansini 5, 80131 Naples, Italy; (C.B.); (F.F.); (I.C.); (M.C.); (M.N.)
- ELFID (European Laboratory for the Investigation of Food-Induced Diseases), University Federico II, Via S. Pansini 5, 80131 Naples, Italy;
| | | |
Collapse
|
|
2
|
Chandra P, Kaleem M, Sachan N, Pathak R, Alanazi AS, Alsaif NA, Alsanea S, Alsuwayt B, Alanazi MM, Kabra A. Gastroprotective evaluation of Medicago sativa L. (Fabaceae) on diabetic rats. Saudi Pharm J 2023; 31:101815. [PMID: 37860685 PMCID: PMC10582054 DOI: 10.1016/j.jsps.2023.101815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Accepted: 10/01/2023] [Indexed: 10/21/2023] Open
Abstract
Traditional uses for the plant Medicago sativa (M. sativa) (Alfalfa) (Family: Fabaceae) include liver protection, antioxidant activity, and the treatment of bleeding and digestive issues. This study aims to assess the effect of ethanol extract of M. sativa (EEMS) on experimental-induced ulcers in diabetic rats. By pylorus ligation and ethanol administration, gastric ulcers were induced in diabetic rats. Five groups each consisting of six rats in each model were used. All other groups except Group I were made diabetic by giving rats alloxan (140 mg/kg i.p.). Vehicles were given to Group I (normal control) and Group II (diabetes control) rats. Group III (positive control) received ranitidine 50 mg/kg, and Group IV and V received EEMS at doses of 100 and 400 mg/kg, respectively. In the pylorus ligation and ethanol-induced stomach ulcer model of rats, the findings demonstrated that EEMS (100 mg/kg) showed a decreased ulcer index of 2.01 ± 0.41 and was found statistically significant against the diabetes control group (p < 0.001) as well as, an ulcer index of 0.68 ± 0.22 by EEMS (400 mg/kg) with a significant reduction in the ulcer index (p < 0.001). EEMS (100 and 400 mg/kg) reduce free acidity by 13.16 ± 0.65 mEq/L and 9.83 ± 0.30 mEq/L, respectively. EEMS also showed a protective impact on the liver and kidneys of diabetic rats. Antihyperglycemic action was also discovered in diabetic animals. The findings of the current investigation demonstrated that ethanolic extract of M. sativa possesses anti-ulcer activity in diabetic rats. Ethanolic extract of M. sativa may be a treatment option for stomach ulcers that also have diabetes.
Collapse
Affiliation(s)
- Phool Chandra
- Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Moradabad, U.P. 244001, India
| | - Mohammad Kaleem
- School of Pharmaceutical Sciences, IFTM University, Lodhipur Rajput, Delhi Road (NH-24), Moradabad 244 102, U.P., India
| | - Neetu Sachan
- Maharana Pratap College of Pharmacy, Mandhana, Kanpur 209217, U.P., India
| | - Rashmi Pathak
- Department of Pharmacy, Invertis University, Bareilly 243123, U.P., India
| | - Ashwag S. Alanazi
- Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia
| | - Nawaf A. Alsaif
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
| | - Sary Alsanea
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Bader Alsuwayt
- Department of Pharmacy Practice, College of Pharmacy, University of Hafr Al-Batin, Hafr Al-Batin 31991, Saudi Arabia
| | - Mohammed M. Alanazi
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
| | - Atul Kabra
- University Institute of Pharma Sciences, Chandigarh University, Mohali 140301, Punjab, India
| |
Collapse
|
|
3
|
Abdu Seid M, Diress M, Mohammed A, Sinamaw D. Chronic constipation and its associated factors in patients with type-2 diabetes: A multicenter cross-sectional study. Diabetes Res Clin Pract 2023; 204:110905. [PMID: 37757985 DOI: 10.1016/j.diabres.2023.110905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 09/04/2023] [Accepted: 09/11/2023] [Indexed: 09/29/2023]
Abstract
INTRODUCTION Diabetes is one of the global public health concern and constipation is frequently seen among gastrointestinal symptoms in diabetes. Despite the fact that constipation is common, doctors and/or patients disregard it. This study aimed to determine the prevalence and contributing factors of constipation in patients with diabetes. METHODS Multi-center cross-sectional study was carried out and the data was analyzed using STATA 14. Binary and multilevel logistic regressions were also carried out to identify associated to factors. Factors having a p-value of less than 0.05 were deemed statistically significant in the final model. RESULTS 206 diabetics participated in the survey. The mean age of the participants was 52.7 years (SD ± 11.9). The prevalence of constipation was 16% (95% CI: 10.97-21.07). Age (AOR = 13.56; 95% CI: 1.71, 107.21), females (AOR = 4.58; 95% CI: 1.76, 11.87), the duration of the diabetes (AOR = 3.16; 95% CI: 1.21, 8.24), and psychological distress (AOR = 12.49, 95% CI: 1.53, 101.8) were significant factors. CONCLUSION The magnitude of constipation was considerable, and it was linked to psychological distress, longer-lasting diabetes, being a woman, and ageing. Patients with type-2 diabetes need to receive careful treatment in order to reduce the severity of the condition and its additional complications.
Collapse
Affiliation(s)
- Mohammed Abdu Seid
- Department of Biomedical Sciences, College of Health Sciences, Debre Tabor University, Ethiopia.
| | | | | | - Deresse Sinamaw
- Department of Biomedical Science, Debre Markos University, Ethiopia.
| |
Collapse
|
|
4
|
Chen J, Yuan S, Fu T, Ruan X, Qiao J, Wang X, Li X, Gill D, Burgess S, Giovannucci EL, Larsson SC. Gastrointestinal Consequences of Type 2 Diabetes Mellitus and Impaired Glycemic Homeostasis: A Mendelian Randomization Study. Diabetes Care 2023; 46:828-835. [PMID: 36800530 PMCID: PMC10091506 DOI: 10.2337/dc22-1385] [Citation(s) in RCA: 47] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Accepted: 01/17/2023] [Indexed: 02/19/2023]
Abstract
OBJECTIVE We conducted a Mendelian randomization (MR) study to examine the associations of type 2 diabetes and glycemic traits with gastrointestinal diseases (GDs). RESEARCH DESIGN AND METHODS Uncorrelated genetic variants associated with type 2 diabetes (n = 231), fasting insulin (n = 38), fasting glucose (n = 71), and hemoglobin A1c (n = 75) at the genome-wide significance were selected as instrument variables. Genetic associations with 23 common GDs were obtained from the FinnGen and UK Biobank studies and other large consortia. RESULTS Genetic liability to type 2 diabetes was associated with the risk of 12 GDs. Per 1-unit increase in the log-transformed odds ratio (OR) of type 2 diabetes, the OR was 1.06 (95% CI, 1.03-1.09) for gastroesophageal reflux disease, 1.12 (95% CI, 1.07-1.17) for gastric ulcer, 1.11 (95% CI, 1.03-1.20) for acute gastritis, 1.07 (95% CI, 1.01-1.13) for chronic gastritis, 1.08 (95% CI, 1.03-1.12) for irritable bowel syndrome, 1.04 (95% CI, 1.01-1.07) for diverticular disease, 1.08 (95% CI, 1.02-1.14) for acute pancreatitis, 1.09 (95% CI, 1.05-1.12) for cholelithiasis, 1.09 (95% CI, 1.05-1.13) for cholelithiasis with cholecystitis, 1.29 (95% CI, 1.17-1.43) for nonalcoholic fatty liver disease, 1.12 (95% CI, 1.03-1.21) for liver cirrhosis, and 0.93 (95% CI, 0.89-0.97) for ulcerative colitis. Genetically predicted higher levels of fasting insulin and glucose were associated with six and one GDs, respectively. CONCLUSIONS Associations were found between genetic liability to type 2 diabetes and an increased risk of a broad range of GDs, highlighting the importance of GD prevention in patients with type 2 diabetes.
Collapse
Affiliation(s)
- Jie Chen
- School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Shuai Yuan
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Tian Fu
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Xixian Ruan
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Jie Qiao
- Department of Endocrinology and Metabolism, the Second Affiliated Hospital of ZheJiang University School of Medicine, Hangzhou, China
| | - Xiaoyan Wang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Xue Li
- School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, U.K
| | - Dipender Gill
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, U.K
| | - Stephen Burgess
- MRC Biostatistics Unit, University of Cambridge, Cambridge, U.K
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, U.K
| | - Edward L. Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA
| | - Susanna C. Larsson
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
- Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| |
Collapse
|
|
5
|
Asghar S, Asghar S, Shahid S, Sajjad H, Abdul Nasir J, Usman M. Gastroparesis-Related Symptoms in Patients With Type 2 Diabetes Mellitus: Early Detection, Risk Factors, and Prevalence. Cureus 2023; 15:e35787. [PMID: 37025723 PMCID: PMC10072787 DOI: 10.7759/cureus.35787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/05/2023] [Indexed: 03/07/2023] Open
Abstract
Background The symptoms of gastroparesis, such as bloating, postprandial fullness, early satiety, nausea, and abdominal discomfort, progressively worsen the quality of life of the affected individuals. The diagnosis is established on the assessment of gastric function that confirms delayed gastric emptying in the absence of structural etiologies. This study aimed to detect gastroparesis-related clinical symptoms early in patients with type 2 diabetes mellitus (T2DM), investigate the concomitant risk factors, and evaluate the prevalence. Methodology This study was conducted at the Department of Medicine and Diabetes Outdoor Clinic of Sheikh Zayed Hospital, Rahim Yar Khan from February 13, 2022, to February 11, 2023. The study involved 175 patients with T2DM who reported gastroparesis-related symptoms. The demographic and clinical characteristics, symptom severity, complications, related risk factors, duration of disease, medications, body mass index (BMI), fasting plasma glucose, and glycated hemoglobin (HbA1C) levels were assessed. The severity of diabetic gastroparesis was established using the disease-specific Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM) and the Gastroparesis Cardinal Symptom Index (GCSI). The five-point scale of the PAGI-SYM and the four-degree severity scores of GCSI were assessed. Neuropathy disability scores and motor evacuation functions were analyzed. Data were analyzed from these questionnaires, special proforma, and patient interviews. Results The clinical features of diabetic gastroparesis were observed in 44% of T2DM patients with mild-grade gastroparesis in 38 (21.7%), moderate in 30 (17.1%), and severe-grade gastroparesis-related symptoms in nine (5.2%) patients. The main manifestations were early satiety (45.1%), stomach fullness (44.5%), bloating (38.3%), and nausea (33.1%). Diabetic gastroparesis symptoms were considerably linked to disease duration of more than 10 years (p = 0.02), high HbA1c (p = 0.001), increased fasting blood glucose (p = 0.003), polyneuropathy, cigarette smoking, and history of comorbid conditions (p = 0.009). Obesity and the female gender were the forecasters of the manifestation of at least one cardinal gastroparesis symptom. Conclusions Gastric emptying is significant in the pathogenesis of gastroparesis-related symptoms. Disease duration of more than 10 years, poor glycemic control with hyperglycemia, high HbA1C, polyneuropathy, and cigarette smoking must be considered as predictors for early detection and risk factors for the advancement of gastroparesis in T2DM. Gastroparesis-related common symptoms of early satiety, bloating, and stomach fullness were considerably linked to the additional risk factors of hypercholesteremia, chronic microvascular complications, concomitant cardiovascular diseases, and a positive family history of diabetes mellitus. There was no relationship between BMI, age, types of treatment, and the degree of gastroparesis severity. The prevalence and severity of gastroparesis symptoms were particularly high among obese females with poor glycemic control and longer disease duration.
Collapse
|
|
6
|
Yuan HL, Zhang X, Peng DZ, Lin GB, Li HH, Li FX, Lu JJ, Chu WW. Development and Validation of a Risk Nomogram Model for Predicting Constipation in Patients with Type 2 Diabetes Mellitus. Diabetes Metab Syndr Obes 2023; 16:1109-1120. [PMID: 37114216 PMCID: PMC10126724 DOI: 10.2147/dmso.s406884] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 04/12/2023] [Indexed: 04/29/2023] Open
Abstract
Purpose Constipation is a common complication of diabetic patients, which has a negative impact on their own health. This study aims to establish and internally validate the risk nomogram of constipation in patients with type 2 diabetes mellitus (T2DM) and to test its predictive ability. Patients and Methods This retrospective study included 746 patients with T2DM at two medical centers. Among the 746 patients with T2DM, 382 and 163 patients in the Beilun branch of the First Affiliated Hospital of Zhejiang University were enrolled in the training cohort and the validation cohort, respectively. A total of 201 patients in the First Affiliated Hospital of Nanchang University were enrolled in external validation cohorts. The nomogram was established by optimizing the predictive factors through univariate and multivariable logistic regression analysis. The prediction performance of the nomogram was measured by the area under the receiver operating characteristic curve (AUROC), the calibration curve, and the decision curve analysis (DCA). Furthermore, its applicability was internally and independently validated. Results Among the 16 clinicopathological features, five variables were selected to develop the prediction nomogram, including age, glycated hemoglobin (HbA1c), calcium, anxiety, and regular exercise. The nomogram revealed good discrimination with an area under the receiver operating characteristic curve (AUROC) of 0.908 (95% CI = 0.865-0.950) in the training cohort, and 0.867 (95% CI = 0.790-0.944) and 0.816 (95% CI = 0.751-0.881) in the internal and external validation cohorts, respectively. The calibration curve presented a good agreement between the prediction by the nomogram and the actual observation. The DCA revealed that the nomogram had a high clinical application value. Conclusion In this study, the nomogram for pretreatment risk management of constipation in patients with T2DM was developed which could help in making timely personalized clinical decisions for different risk populations.
Collapse
Affiliation(s)
- Hai-Liang Yuan
- Department of Gastroenterology, Beilun Branch of the First Affiliated Hospital of Zhejiang University, Ningbo, Zhejiang, People’s Republic of China
| | - Xian Zhang
- Department of Endocrinology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China
| | - Dong-Zhu Peng
- Department of Gastroenterology, Beilun Branch of the First Affiliated Hospital of Zhejiang University, Ningbo, Zhejiang, People’s Republic of China
| | - Guan-Bin Lin
- Department of Gastroenterology, Beilun Branch of the First Affiliated Hospital of Zhejiang University, Ningbo, Zhejiang, People’s Republic of China
| | - Hui-Hui Li
- Department of Gastroenterology, Beilun Branch of the First Affiliated Hospital of Zhejiang University, Ningbo, Zhejiang, People’s Republic of China
| | - Fang-Xian Li
- Department of Gastroenterology, Beilun Branch of the First Affiliated Hospital of Zhejiang University, Ningbo, Zhejiang, People’s Republic of China
| | - Jing-Jing Lu
- Department of Gastroenterology, Beilun Branch of the First Affiliated Hospital of Zhejiang University, Ningbo, Zhejiang, People’s Republic of China
| | - Wei-Wei Chu
- Department of Gastroenterology, Beilun Branch of the First Affiliated Hospital of Zhejiang University, Ningbo, Zhejiang, People’s Republic of China
- Correspondence: Wei-Wei Chu, Department of Gastroenterology, Beilun Branch of the First Affiliated Hospital of Zhejiang University, No. 1288, Lushan East Road, Beilun District, Ningbo, Zhejiang Province, People’s Republic of China, Tel +86-134 56123811, Fax +86- 574 86100266, Email
| |
Collapse
|
|
7
|
Zhang L, Tang F, Wang F, Xie Q, Xia M, Jiang L, Wang ZM, Wang B. The prevalence of constipation in end-stage kidney disease patients: A cross-sectional observation study. Medicine (Baltimore) 2022; 101:e31552. [PMID: 36316834 PMCID: PMC9622587 DOI: 10.1097/md.0000000000031552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
The aim of our study was to determine the prevalence, distribution, and risk factors for constipation in peritoneal dialysis (PD) and hemodialysis (HD) patients in our center. In this cross-sectional study, 858 dialysis patients over 18 years of age (681 HD cases and 177 PD cases from our hospital) were enrolled. A constipation assessment scale (CAS) questionnaire was used to evaluate constipation status. Logistic regression analysis was performed to define independent risk factors for CAS scores. The prevalence of constipation in HD and PD patients was 52.7% and 77.4%, respectively. The mean CAS score in HD and PD patients was 1.73 ± 2.31 and 2.42 ± 2.34, respectively. Age ≥ 65 and diabetic kidney disease for renal failure were independent risk factors associated with constipation in the HD population (OR = 1.67, 95% CI: 1.15-2.90, P = .019; OR = 3.31, 95% CI: 1.65-6.11, P < .001, respectively). In the PD population, only serum prealbumin was independently associated with constipation (OR = 0.88, 95% CI: 0.79-0.96, P = .007). The multivariable logistic regression analysis demonstrated that PD modality, age ≥ 65 and diabetic kidney disease for renal failure were independent risk factors for constipation (OR = 2.15, 95% CI: 1.41-3.32, P < .001; OR = 1.65, 95% CI: 1.13-2.33, P = .003; OR = 3.19, 95% CI: 1.76-5.093, P < .001, respectively). The prevalence of constipation in PD patients was higher than that in HD patients in our center. PD modality for renal replacement therapy, age ≥ 65 and diabetic kidney disease for renal failure were closely associated with constipation in dialysis patients.
Collapse
Affiliation(s)
- Liuping Zhang
- Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China
| | - Fang Tang
- Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China
| | - Fengmei Wang
- Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China
| | - Qinglei Xie
- Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China
| | - Meixia Xia
- Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China
| | - Liangyunzi Jiang
- Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China
| | - Ze-Mu Wang
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Bin Wang
- Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China
- *Correspondence: Bin Wang, Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China (e-mail address: )
| |
Collapse
|
|
8
|
Streptozotocin-Induced Diabetes Causes Changes in Serotonin-Positive Neurons in the Small Intestine in Pig Model. Int J Mol Sci 2022; 23:ijms23094564. [PMID: 35562954 PMCID: PMC9099899 DOI: 10.3390/ijms23094564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 04/19/2022] [Accepted: 04/19/2022] [Indexed: 12/03/2022] Open
Abstract
Serotonin (5-hydroxytryptamine or 5-HT) is an important neurotransmitter of the central and peripheral nervous systems, predominantly secreted in the gastrointestinal tract, especially in the gut. 5-HT is a crucial enteric signaling molecule and is well known for playing a key role in sensory-motor and secretory functions in the gut. Gastroenteropathy is one of the most clinical problems in diabetic patients with frequent episodes of hyperglycemia. Changes in 5-HT expression may mediate gastrointestinal tract disturbances seen in diabetes, such as nausea and diarrhea. Based on the double immunohistochemical staining, this study determined the variability in the population of 5-HT-positive neurons in the porcine small intestinal enteric neurons in the course of streptozotocin-induced diabetes. The results show changes in the number of 5-HT-positive neurons in the examined intestinal sections. The greatest changes were observed in the jejunum, particularly within the myenteric plexus. In the ileum, both de novo 5-HT synthesis in the inner submucosal plexus neurons and an increase in the number of neurons in the outer submucosal plexus were noted. The changes observed in the duodenum were also increasing in nature. The results of the current study confirm the previous observations concerning the involvement of 5-HT in inflammatory processes, and an increase in the number of 5-HT -positive neurons may also be a result of increased concentration of the 5-HT in the gastrointestinal tract wall and affects the motor and secretory processes, which are particularly intense in the small intestines.
Collapse
|
|
9
|
Allemeyer E, Müssig K. Chronische Obstipation und Diabetes mellitus. DIABETOL STOFFWECHS 2021. [DOI: 10.1055/a-1320-9358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
10
|
Bulc M, Całka J, Palus K. Effect of Streptozotocin-Inducted Diabetes on the Pathophysiology of Enteric Neurons in the Small Intestine Based on the Porcine Diabetes Model. Int J Mol Sci 2020; 21:E2047. [PMID: 32192078 PMCID: PMC7139978 DOI: 10.3390/ijms21062047] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Revised: 03/13/2020] [Accepted: 03/14/2020] [Indexed: 12/31/2022] Open
Abstract
Hyperglycemia is one of the main causes of diabetes complications. Gastrointestinal (GI) disturbances are one of the most frequent complications during diabetes. The porcine digestive tract possesses physiological and pathological similarities to the human digestive tract. This also applies to the innervation of the gastrointestinal tract. In this study, the influence of experimentally-inducted hyperglycemia was examined on the expression of vesicular acetylcholine transporter (VAChT), cocaine- and amphetamine-regulated transcript (CART), galanin (GAL), vasoactive intestinal polypeptide (VIP), and calcitonin gene-related peptide (CGRP) in the enteric nervous system (ENS) neurons in the small intestine of the pig. During the current study, an increased number of neurons containing CART, VIP, GAL, and CGRP under streptozotocin injection were observed. The augmentation of expression included all enteric plexuses present in the small intestine. The same results were obtained in the case of VAChT; namely, chronic hyperglycemia led to an increase in the number of neurons utilizing VAChT in all investigated plexuses. The obtained results suggested that the function of neuropeptides studied in this experiment depended on their localization in the ENS structures, as well as part of the GI tract. Diabetes led to alterations in the neurochemical phenotype of small intestine enteric neurons.
Collapse
Affiliation(s)
- Michał Bulc
- Department of Clinical Physiology Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego Str. 13, 10-719 Olsztyn, Poland; (J.C.); (K.P.)
| | | | | |
Collapse
|
|
11
|
Shen X, Zhao Z, Yang B. MicroRNA-155 promotes apoptosis of colonic smooth muscle cells and aggravates colonic dysmotility by targeting IGF-1. Exp Ther Med 2020; 19:2725-2732. [PMID: 32256755 DOI: 10.3892/etm.2020.8485] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Accepted: 06/13/2019] [Indexed: 12/27/2022] Open
Abstract
Colonic dysmotility as a complication of diabetes affects public health; however, the underlying molecular mechanisms have remained elusive. Insulin-like growth factor-1 (IGF-1) was previously demonstrated to prevent apoptosis of colonic smooth muscle cells (SMCs) and alleviate colonic dysmotility in diabetic rats. However, the regulatory mechanisms upstream of IGF-1 in colonic dysmotility have remained to be determined. The present study reports on microRNA-155 (miR-155), initially identified using bioinformatics, as a direct upstream regulator of IGF-1. In colonic SMCs, miR-155 negatively regulated IGF-1 expression at the post-transcriptional level, as identified through ectopic overexpression and knockdown experiments. A luciferase reporter assay further demonstrated that miR-155 inhibits IGF-1 through binding to its 3'-untranslated region. Furthermore, overexpression of miR-155 led to increased apoptosis of colonic SMCs and a decrease in the thickness of colonic smooth muscle tissues of diabetic mice, indicating miR-155 aggravates colonic dysmotility. By contrast, knockdown of miR-155 induced the opposite effect. Overall, the results of the present study suggest a role of miR-155 in colonic dysmotility, thereby providing a novel therapeutic target.
Collapse
Affiliation(s)
- Xiaoxue Shen
- Department of Gastroenterology, Jiangsu Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China
| | - Zhibin Zhao
- Department of Gastroenterology, Jiangsu Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China
| | - Bin Yang
- Department of Gastroenterology, Jiangsu Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China
| |
Collapse
|
|
12
|
Kalkan S, Karatay E, Akbal E. Increased gastrointestinal symptom frequency in diabetes mellitus even with good glycemic control. JOURNAL OF HEALTH SCIENCES AND MEDICINE 2019. [DOI: 10.32322/jhsm.635710] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
|
|
13
|
Effects of diabetes mellitus on myenteric neuronal density and sodium channel expression in the rat ileum. Brain Res 2018; 1708:1-9. [PMID: 30500400 DOI: 10.1016/j.brainres.2018.11.041] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Revised: 11/09/2018] [Accepted: 11/26/2018] [Indexed: 12/25/2022]
Abstract
Diabetes mellitus (DM) may lead to gastrointestinal motility disorders. Rodent models of DM indicate the presence of morpho-functional abnormalities of the enteric nervous system. Here, we evaluated whether experimental DM can cause changes in the excitatory cholinergic fibers, neuronal density, and voltage-gated sodium channel (Nav) expression in the myenteric plexus of the ileum. After streptozotocin-induced hyperglycemia in female rats progressed for eight weeks, triple immunofluorescence labeling experiments revealed that the neuronal density in DM rats was significantly lower than that in control. On average, the density of total neurons reduced by 52.2% (p = 0.0001), cholinergic neurons by 50.0% (p = 0.0068), and nitrergic neurons by 54.8% (p = 0.0042). The number of neurons per ganglionic area was also significantly reduced (to 28.2% of total neurons, p = 0.0002; 27.7% of cholinergic neurons, p = 0.0002, and 32.1% of nitrergic neurons, p = 0.0016). Furthermore, the density of the cholinergic fibers at the surface of the longitudinal muscle was significantly reduced (DM: 24 ± 3%; p = 0.003, control: 41 ± 2%); however, western-blot analysis did not indicate a reduction in the expression of choline acetyltransferase (ChAT) in the DM group. The Nav1.6 isoform was detected in different myenteric neurons of the ileum. RT-qPCR data did not suggest an alteration of transcripts for ChAT, neuronal nitric oxide synthase, Nav1.3, Nav1.6, or Nav1.7. Our data support the view that chronic DM leads to a reduction of excitatory cholinergic fibers and neuronal density. However, changes in sodium channel expression pattern, which could cause neuronal dysfunction, were not detected.
Collapse
|
|
14
|
Ajiboye BO, Oloyede HOB, Salawu MO. Antihyperglycemic and antidyslipidemic activity of Musa paradisiaca-based diet in alloxan-induced diabetic rats. Food Sci Nutr 2018; 6:137-145. [PMID: 29387371 PMCID: PMC5778235 DOI: 10.1002/fsn3.538] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Revised: 08/25/2017] [Accepted: 09/12/2017] [Indexed: 12/19/2022] Open
Abstract
This study was aimed at investigating the antihyperglycemic and antidyslipidemic activity of Musa paradisiaca-based diets in alloxan-induced diabetic mellitus rats. Diabetes was induced by a single intraperitoneal injection of alloxan (150 mg/kg b.w) in 48 randomly selected rats. The rats were randomly grouped into four as follows: normal rats fed Dioscorea rotundata-based diet, diabetic control rats fed D. rotundata-based diet, diabetic rats fed D. rotundata-based diet and administered metformin (14.2 mg/kg body weight) orally per day, and diabetic rats fed M. paradisiaca-based diet. Body weight and fasting blood glucose level were monitored, on 28th days the rats were sacrificed, liver was excised. Thereafter, the hyperglycemic and dyslipidemic statii of the induced diabetic animals were determined. The M. paradisiaca-based diet significantly (p < .05) reversed the levels of fasting blood glucose, with significant (p < .05) increase in insulin and glycogen concentrations. The diet also increased the activity of hexokinase with significant reduction (p < .05) in glucose-6-phosphatase and fructose-1-6-diphosphatase activities. M. paradisiaca-based diet demonstrated significant reduction (p < .05) in cholesterol, triacylglycerol (TG), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and significant increase (p < .05) in high-density lipoprotein (HDL) compared with those of diabetic control group. Also, M. paradisiaca-based diet significantly (p < .05) reversed the activities of aspartate aminotransferase and alanine aminotransferase when compared with diabetic control animals. The consumption of this diet may be useful in ameliorating hyperglycemia and dyslipidemia in diabetes mellitus patients.
Collapse
Affiliation(s)
- Basiru O. Ajiboye
- Department of BiochemistryFaculty of Life SciencesUniversity of IlorinIlorinNigeria
- Department of Chemical SciencesCollege of SciencesAfe Babalola UniversityAdo‐EkitiNigeria
| | | | - Musa O. Salawu
- Department of BiochemistryFaculty of Life SciencesUniversity of IlorinIlorinNigeria
| |
Collapse
|
|
15
|
Bulc M, Palus K, Zielonka Ł, Gajęcka M, Całka J. Changes in expression of inhibitory substances in the intramural neurons of the stomach following streptozotocin- induced diabetes in the pig. World J Gastroenterol 2017; 23:6088-6099. [PMID: 28970724 PMCID: PMC5597500 DOI: 10.3748/wjg.v23.i33.6088] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Revised: 07/19/2017] [Accepted: 08/02/2017] [Indexed: 02/06/2023] Open
Abstract
AIM Influence of chronic hyperglycemia on chemical coding of enteric neurons in stomach using pig as a model for human diabetic complications.
METHODS Ten pigs were divided into two groups: diabetic (D group, n = 5) and control (C group, n = 5). Pigs constituting the experimental group were given streptozotocin (150 mg/kg). Animals were euthanized six weeks after the induction of diabetes. The samples of stomach were collected from animals of both groups. The cryostat sections were processed for double immunofluorescence staining using primary antisera directed towards pan-neuronal marker (Hu C/D) proteins and/or neuronal isoform of nitric oxide synthase (nNOS), vasoactive intestinal peptide (VIP) and galanin (GAL).
RESULTS In the control group in the myenteric ganglia (MG) of the corpus we have noted 22.28% ± 1.19% of nNOS positive neurons, while in diabetic group we have found 40.74% ± 2.22% of nNOS immunoreactive perikarya (increase by 82.85 %). In turn in the pylorus we have observed 15.91% ± 0.58% nNOS containing neurons in control animals and 35.38% ± 1.54% in the diabetes group (increase by 122.37%). In the MG of the antrum and submucosal ganglion (SG) in the corpus hyperglycemia did not cause statistically significant changes. With regard to VIP-positive cell bodies in the antrum MG in the control animals we have noted 18.38 ± 1.39% and 40.74% ± 1.77% in the experimental group (increase by 121.65%). While in the corpus we have observed 23.20% ± 0.23% in the control and 30.93% ± 0.86% in the diabetes group (increase by 33.31%). In turn in the pylorus VIP positive cells bodies constituted 23.64% ± 1.56% in the control group and 31.20% ± 1.10% in the experimental group (increase by 31.97%). In the submucosal ganglion in the corpus we have noted 43.61% ± 1.06% in the control animals and 37.00% ± 1.77% in the experimental group (decrease by 15.15%). Expression of GAL-positive perikarya showed statistically significant changes only in the MG of the antrum and pylorus. In the antrum GAL positive perykarya constituted 26.53% ± 1.52% in the control and 36.67% ± 1.02% in the experimental animals (increase by 38.22%). While in the pylorus GAL positive neurons in the control group constituted 16.32% ± 0.92% and 17.99% ± 0.38% in the experimental animals (increase by 10.23%).
CONCLUSION Our results support the hypothesis that in the course of diabetes, long term episodes of high glucose serum level may influence the chemical phenotyping of enteric neurons.
Collapse
Affiliation(s)
- Michał Bulc
- Department of Clinical Physiology Faculty of Veterinary Medicine, University of Warmia and Mazury, 10-719 Olsztyn, Poland
| | - Katarzyna Palus
- Department of Clinical Physiology Faculty of Veterinary Medicine, University of Warmia and Mazury, 10-719 Olsztyn, Poland
| | - Łukasz Zielonka
- Department of Veterinary Prevention and Feed Hygiene, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-718 Olsztyn, Poland
| | - Magdalena Gajęcka
- Department of Veterinary Prevention and Feed Hygiene, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-718 Olsztyn, Poland
| | - Jarosław Całka
- Department of Clinical Physiology Faculty of Veterinary Medicine, University of Warmia and Mazury, 10-719 Olsztyn, Poland
| |
Collapse
|
|
16
|
Zhao M, Liao D, Zhao J. Diabetes-induced mechanophysiological changes in the small intestine and colon. World J Diabetes 2017; 8:249-269. [PMID: 28694926 PMCID: PMC5483424 DOI: 10.4239/wjd.v8.i6.249] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Revised: 04/05/2017] [Accepted: 05/05/2017] [Indexed: 02/05/2023] Open
Abstract
The disorders of gastrointestinal (GI) tract including intestine and colon are common in the patients with diabetes mellitus (DM). DM induced intestinal and colonic structural and biomechanical remodeling in animals and humans. The remodeling is closely related to motor-sensory abnormalities of the intestine and colon which are associated with the symptoms frequently encountered in patients with DM such as diarrhea and constipation. In this review, firstly we review DM-induced histomorphological and biomechanical remodeling of intestine and colon. Secondly we review motor-sensory dysfunction and how they relate to intestinal and colonic abnormalities. Finally the clinical consequences of DM-induced changes in the intestine and colon including diarrhea, constipation, gut microbiota change and colon cancer are discussed. The final goal is to increase the understanding of DM-induced changes in the gut and the subsequent clinical consequences in order to provide the clinicians with a better understanding of the GI disorders in diabetic patients and facilitates treatments tailored to these patients.
Collapse
|
|
17
|
Costa Gomes R, Cerqueira Maia J, Fernando Arrais R, André Nunes Jatobá C, Auxiliadora Carvalho Rocha M, Edinilma Felinto Brito M, Laissa Oliveira Nazion A, Marques Maranhão C, De Sousa Maranhão H. The celiac iceberg: from the clinical spectrum to serology and histopathology in children and adolescents with type 1 diabetes mellitus and Down syndrome. Scand J Gastroenterol 2016; 51:178-85. [PMID: 26339731 PMCID: PMC4732421 DOI: 10.3109/00365521.2015.1079645] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE The objective of this study is to investigate the occurrence of gastrointestinal (GI) and extraintestinal symptoms in children and adolescents with type 1 diabetes mellitus (DM1) and Down syndrome (DS) and their association with specific antibodies and histopathology of celiac disease (CelD), representing its clinical forms in the iceberg. MATERIAL AND METHODS Cross-sectional study (November 2009-December 2012) conducted at an outpatient care facility in Northeast Brazil including patients [DM1 (n = 111); DS (n = 77)] aged 10 months-18 years old. Measurement of anti-endomysial (EmA) and anti-tissue transglutaminase (anti-tTG) IgA antibodies was performed, as was that of anti-tTG-IgG in the cases with low serum IgA. The patients with antibody positivity were subjected to small intestine biopsy. RESULTS GI symptoms occurred in 53.7% of the sample, extraintestinal symptoms in 4.3%, and antibody positivity in 28.2% (n = 53). Of those who underwent biopsy (n = 40), histopathological findings of CelD were found in 37.5% [DM1 = 5/111 (4.5%), DS = 10/77 (13.0%)]. GI symptoms were associated with antibody positivity, but not with the histopathology. The GI (32.5%), silent (5.0%), and potential (62.5%) forms of disease were detected. CONCLUSIONS The prevalence of GI symptoms was high in groups DM1 and DS, and the occurrence of such symptoms was associated with antibody positivity. The lack of association between the symptoms and histopatholological findings points to the inconsistency of the former as indicators of CelD. Although the GI form predominated among the cases with active CelD, its contribution to the celiac iceberg was smaller compared with the potential form, which determined the large and submerged base of the iceberg representing the high-risk groups investigated.
Collapse
Affiliation(s)
- Rosane Costa Gomes
- Department of Pediatric,Correspondence: Prof. Rosane Costa Gomes,
Department of Pediatric, Federal University of Rio Grande do Norte,
Natal, 59012-310,
Brazil.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
18
|
Zhang M, Yang XJ, Zhu HM, Tang Z, Li BY, Zhao DD. Epidemiological study of elderly constipation in Beijing. World J Gastroenterol 2015; 21:13368-13373. [PMID: 26715822 PMCID: PMC4679771 DOI: 10.3748/wjg.v21.i47.13368] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2015] [Revised: 09/09/2015] [Accepted: 11/13/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the present situation of elderly constipation in urban and rural areas of the Beijing region. METHODS A total of 1942 cases (≥ 60 years) were selected in the Beijing region for investigation. Constipation-related data collection was carried out via hierarchical status, segmentation, and random cluster sampling. Patient data concerning constipation-related demographic indicators, education level, occupation, economic status, and history of gastrointestinal disease was obtained via questionnaires and surveys. Constipation was defined according to the Rome III criteria, with the following constipation judgment indicators: defecation less than 3 times per week, stool weight less than 35 g/d, dry and hard stool, and difficulty in defecating during more than 25% of evacuation attempts. RESULTS Of the 1942 cases, 634 were diagnosed with constipation, and the total prevalence rate was 32.6%, which increased with age. There was a statistically insignificantly higher prevalence of constipation in females (compared to males) and urban areas (compared to rural areas). There was a statistically insignificantly higher prevalence in the illiterate group compared to the literacy group. Those engaged in mental work suffered from statistically significantly higher constipation prevalence than those engaged in physical labor. A total of 1847 cases did not suffer from gastritis, of which 595 cases were constipated; although the prevalence rate was 32.2%, showing a higher incidence of constipation in patients with gastritis, no significant statistical difference between the two groups was found. A total of 59 cases with a past history of biliary tract disease were found, of which 26 had constipation; constipation prevalence was 44.1% (far higher than other groups), which was a statistically significant difference. CONCLUSION The prevalence of elderly constipation in the Beijing region closely resembles Western countries, and is significantly affected by region, age, and past history of other related illnesses.
Collapse
|
|
19
|
da Rosa CVD, Azevedo SCSF, Bazotte RB, Peralta RM, Buttow NC, Pedrosa MMD, de Godoi VAF, Natali MRM. Supplementation with L-Glutamine and L-Alanyl-L-Glutamine Changes Biochemical Parameters and Jejunum Morphophysiology in Type 1 Diabetic Wistar Rats. PLoS One 2015; 10:e0143005. [PMID: 26659064 PMCID: PMC4681705 DOI: 10.1371/journal.pone.0143005] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Accepted: 10/29/2015] [Indexed: 01/01/2023] Open
Abstract
We evaluated the effects of the supplementation with L-glutamine and glutamine dipeptide (GDP) on biochemical and morphophysiological parameters in streptozotocin-diabetic rats. For this purpose, thirty animals were distributed into six groups treated orally (gavage) during thirty days: non diabetic rats (Control) + saline, diabetic + saline; Control + L-glutamine (248 mg/kg), Diabetic + L-glutamine (248 mg/kg), Control + GDP (400 mg/kg), Diabetic + GDP (400 mg/kg). Diabetes was induced by an intravenous injection of streptozotocin (60 mg/kg) and confirmed by fasting glucose ≥ 200 mg/dL. Physiological parameters, i.e., body mass, food intake, blood glucose, water intake, urine and faeces were evaluated during supplementation. After the period of supplementation, the animals were euthanized. The blood was collected for biochemical assays (fructosamine, transaminases, lipid profile, total protein, urea, ammonia). Moreover, the jejunum was excised and stored for morphophysiological assays (intestinal enzyme activity, intestinal wall morphology, crypt proliferative index, number of serotoninergic cells from the mucosa, and vipergic neurons from the submucosal tunica). The physiological parameters, protein metabolism and intestinal enzyme activity did not change with the supplementation with L-glutamine or GDP. In diabetic animals, transaminases and fructosamine improved with L-glutamine and GDP supplementations, while the lipid profile improved with L-glutamine. Furthermore, both forms of supplementation promoted changes in jejunal tunicas and wall morphometry of control and diabetic groups, but only L-glutamine promoted maintenance of serotoninergic cells and vipergic neurons populations. On the other hand, control animals showed changes that may indicate negative effects of L-glutamine. Thus, the supplementation with L-glutamine was more efficient for maintaining intestinal morphophysiology and the supplementation with GDP was more efficient to the organism as a whole. Thus, we can conclude that local differences in absorption and metabolism could explain the differences between the supplementation with L-glutamine or GDP.
Collapse
Affiliation(s)
| | | | - Roberto B. Bazotte
- Department of Pharmacology and Therapeutics, State University of Maringá, Maringá, Paraná, Brazil
| | - Rosane M. Peralta
- Department of Biochemistry, State University of Maringá, Maringá, Paraná, Brazil
| | - Nilza C. Buttow
- Department of Morphological Sciences, State University of Maringá, Maringá, Paraná, Brazil
| | | | - Vilma A. F. de Godoi
- Department of Physiological Sciences, State University of Maringá, Maringá, Paraná, Brazil
| | - Maria Raquel M. Natali
- Department of Morphological Sciences, State University of Maringá, Maringá, Paraná, Brazil
- * E-mail: (MR)
| |
Collapse
|
|
20
|
Faria M, Pavin EJ, Parisi MCR, Nagasako CK, Mesquita MA. Dyspeptic symptoms in patients with type 1 diabetes: endoscopic findings, Helicobacter pylori infection, and associations with metabolic control, mood disorders and nutritional factors. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2015; 59:129-36. [PMID: 25993675 DOI: 10.1590/2359-3997000000025] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/24/2014] [Accepted: 12/03/2014] [Indexed: 12/31/2022]
Abstract
OBJECTIVES To evaluate, in a group of patients with long-standing type 1 diabetes (DM1), an association of dyspepsia symptoms with: changes in the gastroduodenal mucosa, infection by Helicobacter pylori, glycemic control, and psychological and nutritional factors. SUBJECTS AND METHODS A total of 32 patient with DM1 were studied (age: 38 ± 9 years; females: 25; diabetes duration: 22 ± 5 years). All patients answered a standardized questionnaire for the evaluation of gastrointestinal symptoms and underwent upper gastrointestinal endoscopy, with gastric biopsies for the evaluation of Helicobacter pylori infection. The presence of anxiety and depression was evaluated by the HAD scale. Nutritional parameters were BMI, arm and waist circumference, skinfold measurement, and body fat percentage. RESULTS Upper endoscopy detected lesions in the gastric mucosa in 34.4% of the patients, with similar frequency in those with (n = 21) and without dyspepsia (n = 11). The patients with dyspepsia complaints showed greater frequency of depression (60% vs. 0%; p = 0.001), higher values for HbA1c (9.6 ± 1.7 vs. 8.2 ± 1.3%; p = 0.01) and lower values for BMI (24.3 ± 4.1 vs. 27.2 ± 2.6 kg/m2; p = 0.02), body fat percentage (26.6 ± 6.2 vs. 30.8 ± 7.7%; p = 0.04), and waist circumference (78.7 ± 8 vs. 85.8 ± 8.1 cm; p = 0.02). No association was found between the symptoms and the presence of Helicobacter pylori. CONCLUSIONS Dyspepsia symptoms in patients with long-standing DM1 were associated with glycemic control and depression, and they seem to negatively influence the nutritional status of these patients.
Collapse
Affiliation(s)
- Mariza Faria
- Department of Clinical Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil
| | | | | | | | - Maria Aparecida Mesquita
- Department of Clinical Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil
| |
Collapse
|
|
21
|
Chen Y, Zheng Y, Shi HL, Fei XY, Yuan JY. Relationship between ghrelin and abnormal gastric emptying in diabetes mellitus. Shijie Huaren Xiaohua Zazhi 2014; 22:5298-5303. [DOI: 10.11569/wcjd.v22.i34.5298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
In recent years, the morbidity of diabetes mellitus has increased rapidly in the world, and the harm of complications of diabetes mellitus has ranked third after cancer and cardiovascular and cerebrovascular diseases. Abnormal gastric emptying is one of the common complications of diabetic mellitus, which seriously influences the life quality of the patients. Therefore, it is important to investigate the pathogenesis of abnormal gastric emptying in diabetes mellitus. The role of ghrelin in the pathophysiology of abnormal gastric emptying in diabetes mellitus is a hot area of research now. In this paper, we review the relationship between ghrelin and abnormal gastric emptying in diabetes mellitus.
Collapse
|
|
22
|
Sun M, Wang F, Feng P. Insulin-like growth factor-1 inhibits colonic smooth muscle cell apoptosis in diabetic rats with colonic dysmotility. ACTA ACUST UNITED AC 2014; 194-195:41-8. [PMID: 25450576 DOI: 10.1016/j.regpep.2014.11.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2014] [Revised: 11/04/2014] [Accepted: 11/11/2014] [Indexed: 02/08/2023]
Abstract
Cellular apoptosis and colonic dysmotility are involved in diabetes mellitus (DM) complications. Insulin-like growth factor-1 (IGF-1) is known to affect apoptosis and proliferation. Here, we demonstrated that the treatment of 1500 ng/kg IGF-1 partly recovers the decrease of the muscle thickness, body weight and gastrointestinal transit rate in DM rats. The gastrointestinal transit rate is positively correlated with the IGF-I level, but negatively correlated with the level of colonic cellular apoptosis. The DM-induced colonic apoptosis is also attenuated by the IGF-1 stimulation. Moreover, IGF-1 inhibits the apoptosis of the isolated colonic SMCs in vitro via the activation of PI3K/Akt and ERK1/2 signaling pathways. Taken together, our data indicated that IGF-1 inhibits the DM-induced colonic SMC apoptosis and might be involved in the alleviation of colonic dysmotility in diabetic rats.
Collapse
Affiliation(s)
- Manyi Sun
- Department of Metabolic Diseases, Tianjin Medical University General Hospital, Tianjin 300052, China; Department of Gastroenterology, Tianjin Union Medicine Center, Tianjin 300121, China
| | - Feng Wang
- Department of Gastroenterology and Digestive Endoscopy, Tianjin Union Medicine Center & Tianjin People's Hospital, Tianjin 300121, China
| | - Ping Feng
- Department of Metabolic Diseases, Tianjin Medical University General Hospital, Tianjin 300052, China.
| |
Collapse
|
|
23
|
Chen X, Fu XS, Li CP, Zhao HX. ER stress and ER stress-induced apoptosis are activated in gastric SMCs in diabetic rats. World J Gastroenterol 2014; 20:8260-8267. [PMID: 25009401 PMCID: PMC4081701 DOI: 10.3748/wjg.v20.i25.8260] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2014] [Revised: 03/04/2014] [Accepted: 04/09/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the gastric muscle injury caused by endoplasmic reticulum (ER) stress in rats with diabetic gastroparesis.
METHODS: Forty rats were randomly divided into two groups: a control group and a diabetic group. Diabetes was induced by intraperitoneal injection of 60 mg/kg of streptozotocin. Gastric emptying was determined at the 4th and 12th week. The ultrastructural changes in gastric smooth muscle cells (SMCs) were investigated by transmission electron microscopy. TdT-mediated dUTP nick end labeling (TUNEL) assay was performed to assess apoptosis of SMCs. Expression of the ER stress marker, glucose-regulated protein 78 (GRP78), and the ER-specific apoptosis mediator, caspase-12 protein, was determined by immunohistochemistry.
RESULTS: Gastric emptying was significantly lower in the diabetic rats than in the control rats at the 12th wk (40.71% ± 2.50%, control rats vs 54.65% ± 5.22%, diabetic rats; P < 0.05). Swollen and distended ER with an irregular shape was observed in gastric SMCs in diabetic rats. Apoptosis of gastric SMCs increased in the diabetic rats in addition to increased expression of GRP78 and caspase-12 proteins.
CONCLUSION: ER stress and ER stress-mediated apoptosis are activated in gastric SMCs in diabetic rats with gastroparesis.
Collapse
|
|
24
|
Roslani AC, Ramakrishnan R, Azmi S, Arapoc DJ, Goh A. Prevalence of faecal incontinence and its related factors among patients in a Malaysian academic setting. BMC Gastroenterol 2014; 14:95. [PMID: 24885285 PMCID: PMC4029879 DOI: 10.1186/1471-230x-14-95] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2013] [Accepted: 05/07/2014] [Indexed: 11/10/2022] Open
Abstract
Background Prevalence data is essential for planning of healthcare services. The prevalence of faecal incontinence (FI) varies worldwide, and in Malaysia is not known. We sought to estimate its prevalence among patients with various conditions in a Malaysian academic setting. Method A questionnaire-based survey was conducted among a convenience sample of adult patients and relatives who visited the Obstetrics and Gynaecology and General Surgery Clinics of University of Malaya Medical Centre (UMMC) from June 2009 to February 2010. Data collected included patient demographics and pre-existing medical conditions known to be FI risk factors. Severity of FI was assessed using the Wexner Continence Scale (WCS). Results Among the 1000 subjects recruited into the study, 760 (76%) were female and the median age was 38 years with an inter-quartile range of 24 years. The prevalence of FI among the study subjects was found to be 8.3%. Among them, 63 subjects (75.9%) were determined to have mild FI as measured by the WCS. The proportions of patients with moderate and severe FI were 18.3% and 6.0%, respectively. FI was found to be significantly associated with older age, presence of diabetes mellitus and increased duration of defaecation. There was no statistically significant association between FI and sex, defaecation frequency, or history of surgery. Conclusion FI in our setting is prevalent enough to warrant targeted healthcare interventions, including the need to improve general public awareness of the condition in order to counter social stigma and embarrassment that may be faced by patients.
Collapse
Affiliation(s)
- April C Roslani
- Department of Surgery, University of Malaya Medical Centre, Kuala Lumpur, Malaysia.
| | | | | | | | | |
Collapse
|
|
25
|
Is L-glutathione more effective than L-glutamine in preventing enteric diabetic neuropathy? Dig Dis Sci 2014; 59:937-48. [PMID: 24370785 DOI: 10.1007/s10620-013-2993-2] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2013] [Accepted: 12/10/2013] [Indexed: 12/13/2022]
Abstract
BACKGROUND Diabetes and its complications appear to be multifactorial. Substances with antioxidant potential have been used to protect enteric neurons in experimental diabetes. AIM This study evaluated the effects of supplementation with L-glutamine and L-glutathione on enteric neurons in the jejunum in diabetic rats. METHODS Rats at 90 days of age were distributed into six groups: normoglycemic, normoglycemic supplemented with 2 % L-glutamine, normoglycemic supplemented with 1 % L-glutathione, diabetic (D), diabetic supplemented with 2 % L-glutamine (DG), and diabetic supplemented with 1 % L-glutathione (DGT). After 120 days, the jejunums were immunohistochemically stained for HuC/D+ neuronal nitric oxide synthase (nNOS) and vasoactive intestinal polypeptide (VIP). Western blot was performed to evaluate nNOS and VIP. Submucosal and myenteric neurons were quantitatively and morphometrically analyzed. RESULTS Diabetic neuropathy was observed in myenteric HuC/D, nNOS, and VIP neurons (p < 0.05). In the submucosal plexus, diabetes did not change nitrergic innervation but increased VIPergic neuronal density and body size (p < 0.05). Supplementation with L-glutathione prevented changes in HuC/D neurons in the enteric plexus (p < 0.05), showing that supplementation with L-glutathione was more effective than with L-glutamine. Myenteric nNOS neurons in the DGT group exhibited a reduced density (34.5 %) and reduced area (p < 0.05). Submucosal neurons did not exhibit changes. The increase in VIP-expressing neurons was prevented in the submucosal plexus in the DG and DGT groups (p < 0.05). CONCLUSION Supplementation with L-glutathione exerted a better neuroprotective effect than L-glutamine and may prevent the development of enteric diabetic neuropathy.
Collapse
|
|
26
|
Yang W, Wang N, Shi X, Chen J. Synchronized dual pulse gastric electrical stimulation induces activation of enteric glial cells in rats with diabetic gastroparesis. Gastroenterol Res Pract 2014; 2014:964071. [PMID: 24860604 PMCID: PMC4003764 DOI: 10.1155/2014/964071] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2014] [Revised: 03/09/2014] [Accepted: 03/10/2014] [Indexed: 12/23/2022] Open
Abstract
Objective. The aims of this study were to investigate the effects of synchronized dual pulse gastric electrical stimulation (SGES) on gastric motility in different periods for diabetic rats and try to explore the possible mechanisms of the effects. Methods. Forty-six rats were used in the study. Gastric slow waves were recorded at baseline, 7-14-day diabetes and 56-63-day diabetes before and after stimulation and the age-matched control groups. SGES-60 mins and SGES-7 days (60 mins/day) were performed to test the effects on gastric motility and to evaluate glial marker S100B expression in stomach. Results. (1) Gastric emptying was accelerated in 7-14-day diabetes and delayed in 56-63-day diabetes. (2) The S100B expression in 56-63-day diabetes decreased and the ultrastructure changed. (3) The age-associated loss of EGC was observed in 56-63-day control group. (4) SGES was able to not only accelerate gastric emptying but also normalize gastric slow waves. (5) The S100B expression increased after SGES and the ultrastructure of EGC was partially restored. The effect of SGES-7 days was superior to SGES-60 mins. Conclusions. Delayed gastric emptying due to the growth of age may be related to the EGC inactivation. The effects of the SGES on gastric motility may be associated with EGC activation.
Collapse
Affiliation(s)
- Wei Yang
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Nian Wang
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Xue Shi
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Jie Chen
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| |
Collapse
|
|
27
|
Chen Y, Xu JJ, Liu S, Hou XH. Electroacupuncture at ST36 ameliorates gastric emptying and rescues networks of interstitial cells of Cajal in the stomach of diabetic rats. PLoS One 2013; 8:e83904. [PMID: 24391842 PMCID: PMC3877115 DOI: 10.1371/journal.pone.0083904] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2013] [Accepted: 11/08/2013] [Indexed: 01/18/2023] Open
Abstract
Depletion of interstitial cells of Cajal (ICC) is certified in the stomach of diabetic patients. Though electroacupuncture (EA) at ST36 is an effective therapy to regulate gastric motility, the mechanisms of EA at ST36 on gastric emptying and networks of ICC remain to be elucidated. The aims of this study were to investigate the effects of EA on gastric emptying and on the alterations of ICC networks. Rats were randomized into the control, diabetic rats (DM), diabetic rats with sham EA (DM+SEA), diabetic rats with low frequency EA (DM+LEA) and diabetic rats with high frequency EA groups (DM+HEA). The expression of c-kit in each layer of gastric wall was assessed by western blotting. The proliferation of ICC was identified by immunolabeling of c-kit and Ki67 as the apoptosis of ICC was examined by TUNEL staining. The results were as follows: (1) Gastric emptying was severely delayed in the DM group, but accelerated in the LEA and HEA group, especially in the LEA group. (2) The expression of c-kit in each layer was reduced apparently in the DM group, but also up-regulated in the LEA and HEA group. (3) Plentiful proliferated ICC (c-kit+/Ki67+) forming bushy networks with c-kit+ cells were observed in the LEA and HEA group, while the apoptotic cells (c-kit+/TUNEL+) were hardly captured in the LEA and HEA group. Collectively, low and high frequency EA at ST36 rescue the damaged networks of ICC by inhibiting the apoptosis and enhancing the proliferation in the stomach of diabetic rats, resulting in an improved gastric emptying.
Collapse
Affiliation(s)
- Yan Chen
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Juan Juan Xu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shi Liu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiao Hua Hou
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| |
Collapse
|
|
28
|
Graversen C, Frøkjaer JB, Brock C, Drewes AM, Farina D. Support vector regression correlates single-sweep evoked brain potentials to gastrointestinal symptoms in diabetes mellitus patients. ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2013; 2012:5242-5. [PMID: 23367111 DOI: 10.1109/embc.2012.6347176] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Diabetes mellitus (DM) is a multi-factorial and complex disease causing autonomic neuropathy and gastrointestinal symptoms in some patients. The neural mechanisms behind these symptoms are poorly understood, but it is believed that both peripheral and central mechanisms are involved. To gain further knowledge of the central mechanisms, the aim of this study was to identify biomarkers for the altered brain activity in type-1 DM patients compared to healthy volunteers (HV), and to correlate the obtained biomarkers to clinical patient scores. The study included 14 DM patients and 15 HV, with brain activity recorded as multi-channel electroencephalography evoked brain potentials (EPs) elicited by painful electrical stimulations in the esophagus. The single-sweep EPs were decomposed by an optimized discrete wavelet transform (DWT), and averaged for each channel. The DWT features from the DM patients were discriminated from the HV by a support vector machine (SVM) applied in regression mode. For the optimal DWT, the discriminative features were extracted and the SVM regression value representing the overall alteration of the EP was correlated to the clinical scores. A classification performance of 86.2% (P=0.01) was obtained by applying a majority voting scheme to the 5 best performing channels. The biomarker was identified as decreased theta band activity. The regression value was correlated to symptoms reported by the patients (P=0.04). The methodology is an improvement of the present approach to study central mechanisms in diabetes mellitus, and may provide a future application for a clinical tool to optimize treatment in individual patients.
Collapse
Affiliation(s)
- C Graversen
- Mech-Sense, Department of Gastroenterology & Radiology, Aalborg Hospital, DK-9000 Aalborg, Denmark.
| | | | | | | | | |
Collapse
|
|
29
|
Wang Y, Xu XY, Tang YR, Yang WW, Yuan YF, Ning YJ, Yu YJ, Lin L. Effect of endogenous insulin-like growth factor and stem cell factor on diabetic colonic dysmotility. World J Gastroenterol 2013; 19:3324-3331. [PMID: 23745035 PMCID: PMC3671085 DOI: 10.3748/wjg.v19.i21.3324] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2013] [Revised: 03/23/2013] [Accepted: 04/19/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate whether the reduction of stem cell factor (SCF) is mediated by decreased endogenous insulin-like growth factor (IGF)-1 in diabetic rat colon smooth muscle.
METHODS: Sixteen Sprague-Dawley rats were randomly divided into two groups: control group and streptozotocin-induced diabetic group. After 8 wk of streptozotocin administration, colonic motility function and contractility of circular muscle strips were measured. The expression of endogenous IGF-1 and SCF was tested in colonic tissues. Colonic smooth muscle cells were cultured from normal adult rats. IGF-1 siRNA transfection was used to investigate whether SCF expression was affected by endogenous IGF-1 expression in smooth muscle cells, and IGF-1 induced SCF expression effects were studied. The effect of high glucose on the expression of endogenous IGF-1 and SCF was also investigated.
RESULTS: Diabetic rats showed prolonged colonic transit time (252 ± 16 min vs 168 ± 9 min, P < 0.01) and weakness of circular muscle contraction (0.81 ± 0.09 g vs 2.48 ± 0.23 g, P < 0.01) compared with the control group. Endogenous IGF-1 and SCF protein expression was significantly reduced in the diabetic colonic muscle tissues. IGF-1 and SCF mRNA expression also showed a paralleled reduction in diabetic rats. In the IGF-1 siRNA transfected smooth muscle cells, SCF mRNA and protein expression was significantly decreased. IGF-1 could induce SCF expression in a concentration and time-dependent manner, mainly through the extracellular-signal-regulated kinase 1/2 signal pathway. High glucose inhibited endogenous IGF-1 and SCF expression and the addition of IGF-1 to the medium reversed the SCF expression.
CONCLUSION: Myopathy may resolve in colonic motility dysfunction in diabetic rats. Deficiency of endogenous IGF-1 in colonic smooth muscle cells leads to reduction of SCF expression.
Collapse
MESH Headings
- Animals
- Blood Glucose/metabolism
- Cells, Cultured
- Colon/metabolism
- Colon/physiopathology
- Diabetes Mellitus, Experimental/complications
- Diabetes Mellitus, Experimental/genetics
- Diabetes Mellitus, Experimental/metabolism
- Diabetes Mellitus, Experimental/physiopathology
- Down-Regulation
- Gastrointestinal Transit
- Insulin-Like Growth Factor I/genetics
- Insulin-Like Growth Factor I/metabolism
- Male
- Mitogen-Activated Protein Kinase 1/metabolism
- Mitogen-Activated Protein Kinase 3/metabolism
- Muscle Contraction
- Muscle, Smooth/metabolism
- Muscle, Smooth/physiopathology
- Myocytes, Smooth Muscle/metabolism
- RNA Interference
- RNA, Messenger/metabolism
- RNA, Small Interfering/metabolism
- Rats
- Rats, Sprague-Dawley
- Signal Transduction
- Stem Cell Factor/genetics
- Stem Cell Factor/metabolism
- Time Factors
- Transfection
Collapse
|
|
30
|
Zhang J, Huang C, Li Y, Chen J, Shen F, Yao Q, Qian J, Bao B, Yao X. Health-related quality of life in dialysis patients with constipation: a cross-sectional study. Patient Prefer Adherence 2013; 7:589-94. [PMID: 23814466 PMCID: PMC3693922 DOI: 10.2147/ppa.s45471] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
OBJECTIVES To evaluate differences in the health-related quality of life (HRQoL) between patients with constipation receiving hemodialysis (HD) and those receiving peritoneal dialysis (PD). METHODS In this cross-sectional study, 605 dialysis patients (478 HD cases and 127 PD cases; all patients were older than 18 years) from our hospital were included. A questionnaire was used to evaluate their constipation statuses. The effect of constipation on HRQoL was assessed, using the Chinese version of the 12-item short-form (SF-12) general health survey. Karnofsky score, sociodemographic, and clinical data were also collected. We performed multiple logistic regression analysis to define independent risk factors for constipation and impaired HRQoL. RESULTS A total of 605 participants (326 men [53.9%] and 279 women [46.1%]) were surveyed. The incidence of constipation was 71.7% in HD patients and 14.2% in PD patients. Dialysis patients with constipation had significantly lower mean SF-12 Physical Component Summary scale and Mental Component Summary scale scores than the nonconstipation group (P < 0.05), whereas HD patients had better SF-12 Physical Component Summary and Mental Component Summary scores than PD patients (P < 0.05). When we performed multivariate logistic regression analysis, dialysis modality, diabetes, and the number of constipation-related medications were three independent risk factors associated with constipation. As for impaired HRQoL in the constipated dialysis population, dialysis modality was found to be another independent risk factor in addition to age and diabetes. CONCLUSION PD patients with constipation had worse HRQoL than HD control participants. We should pay more attention to the patients with constipation receiving PD, as peritonitis caused by constipation was associated with a higher mortality.
Collapse
Affiliation(s)
- JiSheng Zhang
- Division of Nephrology, School of Medicine, Ningbo Urology and Nephrology Hospital, Ningbo University, Ningbo, Zhejiang, People’s Republic of China
| | - CongYang Huang
- Division of Nephrology, School of Medicine, Ningbo Urology and Nephrology Hospital, Ningbo University, Ningbo, Zhejiang, People’s Republic of China
| | - YanLi Li
- Division of Nephrology, School of Medicine, Ningbo Urology and Nephrology Hospital, Ningbo University, Ningbo, Zhejiang, People’s Republic of China
| | - Jun Chen
- Blood Purification Center, School of Medicine, Ningbo Urology and Nephrology Hospital, Ningbo University, Ningbo, Zhejiang, People’s Republic of China
| | - FangYuan Shen
- Division of Nephrology, School of Medicine, Ningbo Urology and Nephrology Hospital, Ningbo University, Ningbo, Zhejiang, People’s Republic of China
| | - Qiang Yao
- Baxter Healthcare Pty Ltd, Shanghai, People’s Republic of China
| | - JiaQi Qian
- Division of Nephrology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - BeiYan Bao
- Division of Nephrology, School of Medicine, Ningbo Urology and Nephrology Hospital, Ningbo University, Ningbo, Zhejiang, People’s Republic of China
- Correspondence: BeiYan Bao, Division of Nephrology, School of Medicine, Ningbo Urology and Nephrology Hospital, Ningbo University, Ningbo, Zhejiang, People’s Republic of China Tel +86 574 8303 9291 Fax +86 574 8303 8510 Email
| | - XuPing Yao
- Division of Urology, School of Medicine, Ningbo Urology and Nephrology Hospital, Ningbo University, Ningbo, Zhejiang, People’s Republic of China
| |
Collapse
|