Diabetes is characterized by insulin resistance as well as impaired insulin production, with β-cell dysfunction playing a critical role in disease progression. Exercise is known to improve insulin sensitivity, but its effects on pancreatic islet quality and function remain poorly understood. This work hypothesized that swimming training enhances glycemic control and insulin secretion by upregulating the insulin-like growth factor 1 (IGF-1)/phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway in streptozotocin (STZ)-induced diabetic rats.

To investigate the effects of swimming on pancreatic islet quality and function in STZ-induced diabetic rats via the IGF-1/PI3K/AKT pathway.

Twenty-six Sprague-Dawley rats were grouped into diabetic and control groups, with each group further split into exercise and sedentary subgroups. Diabetic rats were induced with STZ. The exercise groups underwent swimming training for 60 minutes/day, 5 days/week, for 8 weeks. Body weight, food intake, blood glucose, insulin, lipids, and muscle glycogen were measured. Pancreatic islet morphology and the protein expression levels of IGF-1, PI3K, and AKT were analyzed. Data were analyzed using two-way repeated-measure ANOVA, followed by Tukey’s post-hoc test.

Exercise training significantly improved body weight [diabetic exercise group (D-Ex): 390.66 ± 50.14 g vs diabetic sedentary group (D-Sed): 315.89 ± 50.12 g, P < 0.05], reduced blood glucose (D-Ex: 12.21 ± 4.43 mmol/L vs D-Sed: 17.79 ± 2.05 mmol/L, P < 0.05), and increased insulin levels (D-Ex: 53.50 ± 15.31 pmol/L vs D-Sed: 25.31 ± 10.23 pmol/L, P < 0.05) in diabetic rats. It also enhanced islet morphology, increased IGF-1 expression, and activated the PI3K/AKT pathway (P < 0.05). In-vitro experiments confirmed that IGF-1 positively regulated insulin expression and inhibited β-cell apoptosis via the PI3K/AKT pathway.

Exercise training improves pancreatic islet quality and function in diabetic rats by modulating the IGF-1/PI3K/AKT pathway, highlighting its therapeutic potential for diabetes management.

• Exercise training
• Diabetes
• Insulin-like growth factor 1
• Phosphatidylinositol 3-kinase/protein kinase B
• Islet

• Diabetes
• GIP
• GLP-1
• Incretin
• Insulin
• Obesity

• Gastric Inhibitory Polypeptide/metabolism
• Gastric Inhibitory Polypeptide/therapeutic use
• Humans
• Animals
• Receptors, Gastrointestinal Hormone/metabolism
• Incretins/metabolism
• Glucagon-Like Peptide 1/metabolism
• Obesity/metabolism
• Obesity/drug therapy
• Diabetes Mellitus/metabolism
• Diabetes Mellitus/drug therapy

• Antidiabetic drugs
• Insulin secretion
• Pancreatic β‐cell

• Humans
• Diabetes Mellitus, Type 2/drug therapy
• Diabetes Mellitus, Type 2/metabolism
• Insulin-Secreting Cells/drug effects
• Insulin-Secreting Cells/metabolism
• Insulin-Secreting Cells/physiology
• Hypoglycemic Agents/therapeutic use
• Animals

• 2021R1C1C1009875 National Research Foundation of Korea
• National Research Foundation of Korea

• CAM
• GIPR
• MK0893
• RB
• TFF1
• gastric inhibitory polypeptide receptor
• miR-542-5p
• retinoblastoma
• trefoil factor family peptide
• tumorigenesis

• antidiabetics
• antioxidants
• diabetes mellitus
• incretin hormone
• medicinal plants

• Animals
• Humans
• Dipeptidyl-Peptidase IV Inhibitors/pharmacology
• Dipeptidyl-Peptidase IV Inhibitors/therapeutic use
• Dipeptidyl Peptidase 4/metabolism
• Blood Glucose/metabolism
• Plants, Medicinal
• Hypoglycemic Agents/pharmacology
• Hypoglycemic Agents/therapeutic use
• Diabetes Mellitus, Type 2/drug therapy
• Glucagon-Like Peptide 1/therapeutic use

• Des-fluoro-sitagliptin
• Exendin-4
• Fructose-rich diet
• GLP-1 receptor agonist
• Inflammation
• Liver fructokinase
• Oxidative stress
• Prediabetes

Dipeptidyl peptidase 4 (DPP4) is a molecule implicated in the regulation of metabolic homeostasis and inflammatory processes, and it exerts its main action through its enzymatic activity. DPP4 represents the enzyme most involved in the catabolism of incretin hormones; thus, its activity impacts appetite, energy balance, and the fine regulation of glucose homeostasis. Indeed, DPP4 inhibitors represent a class of antidiabetic agents widely used for the treatment of Type 2 diabetes mellitus (T2DM). DPP4 also acts as an adipokine and is mainly secreted by the adipose tissue, mostly from mature adipocytes of the visceral compartment, where it exerts autocrine and paracrine activities. DPP4 can disrupt insulin signaling within the adipocyte and in other target cells and tissues, where it also favors the development of a proinflammatory environment. This is likely at the basis of the presence of elevated circulating DPP4 levels in several metabolic diseases. In this review, we summarize the most recent evidence of the role of the DPP4 as an adipokine-regulating glucose/insulin metabolism and fat homeostasis, with a particular focus on clinical outcomes associated with its increased secretion in the presence of adipose tissue accumulation and dysfunction.

• Diabetes
• Glucose tolerance
• Melatonin
• Sitagliptin
• β-Cell regeneration

Background: To verify whether, in patients on metformin (MET) monotherapy for type 2 diabetes (T2D), the add-on of a dipeptidyl peptidase inhibitor (DPP4i) compared to a sulfonylurea (SU) can delay the time to the subsequent treatment intensification (TI).

Methods: Population-based administrative data banks from four Italian geographic areas were used. Patients aged ≥18 years on MET monotherapy receiving first DPP4i or SU dispensing between 2008 and 2015 (cohort entry) were followed up to the occurrence of TI (insulin dispensing or add-on of a third non-insulin hypoglicemic >180 days after cohort entry), treatment discontinuation, switch, cancer, death, TI occurrence within, end of data availability, end of study period (31 December 2016), whichever came first. Patients on MET + DPP4i were matched 1:1 with those on MET + SU by sex, age, year of cohort entry, and data bank. Hazard Ratio (HR) and 95% confidence intervals (95%CI) were estimated using multivariable Cox regression model including matching variables and potential confounders measured at baseline. Different sensitivity analyses were performed: i) matching at 180 days after cohort entry, ii) intent to treat (ITT) analysis, iii) matching by duration of MET monotherapy, iv) matching by propensity score.

Results: The matched study cohort included 10,600 patients. Overall, 763 TI were observed (4.5/100 person-years; mean follow-up = 1.6 years). The primary analysis showed no difference in time to TI between the two groups (HR = 1.02; 95% CI = 0.88–1.19). Sensitivity analyses confirmed this result, except from the ITT analysis (HR = 1.27; 1.13–1.43).

Conclusion: The use of a DPP4i rather than a SU as add-on to MET monotherapy was not associated with a delay in treatment intensification.

• cardiovascular diseases
• diabetes
• fish peptides
• metabolic syndrome
• obesity

• SGLT2
• SGLT2 inhibitors
• chronic kidney disease
• diabetes
• heart failure

• Cardiovascular System/metabolism
• Diabetes Mellitus, Type 2/drug therapy
• Diabetes Mellitus, Type 2/metabolism
• Glucose/therapeutic use
• Humans
• Sodium/metabolism
• Sodium-Glucose Transporter 2/metabolism
• Sodium-Glucose Transporter 2 Inhibitors/pharmacology
• Sodium-Glucose Transporter 2 Inhibitors/therapeutic use

• Project RVO-VFN64165 General University Hospital in Prague

• DPP-4 inhibitor
• GABA
• NOD mice
• PPI
• insulin
• type 1 diabetes (or diabetes)

• Animals
• Mice
• C-Peptide
• Diabetes Mellitus, Experimental/drug therapy
• Diabetes Mellitus, Type 1/drug therapy
• Dipeptidyl-Peptidase IV Inhibitors
• gamma-Aminobutyric Acid/therapeutic use
• Hypoglycemic Agents/therapeutic use
• Mice, Inbred NOD
• Omeprazole/therapeutic use
• Proton Pump Inhibitors/therapeutic use
• Sitagliptin Phosphate/therapeutic use

• Vetenskapsrådet
• Novo Nordisk Fonden

• Biological activities
• Furoquinolones
• Heteroannulation
• Oxazoloquinolones
• Pyranoquinolones
• Pyrroloquinolones
• Thienoquinolones

• Dipeptidyl peptidase 4
• Dipeptidyl peptidase-4 inhibitor
• Dipeptidyl peptidase-4 substrate
• Mesenchymal stem-cells
• Regenerative medicine
• Wound healing

• Biology
• Dipeptidyl Peptidase 4/metabolism
• Dipeptidyl-Peptidase IV Inhibitors/adverse effects
• Humans
• Incretins/metabolism
• Regenerative Medicine

Type 2 diabetes (T2DM) is characterized by insulin resistance and β-cell dysfunction. Because patients with T2DM have inadequate β-cell mass (BCM) and β-cell dysfunction worsens glycemic control and makes treatment difficult, therapeutic strategies to preserve and restore BCM are needed. In rodent models, obesity increases BCM about 3-fold, but the increase in BCM in humans is limited. Besides, obesity-induced changes in BCM may show racial differences between East Asians and Caucasians. Recently, the developmental origins of health and disease hypothesis, which states that the risk of developing noncommunicable diseases including T2DM is influenced by the fetal environment, has been proposed. It is known in rodents that animals with low birthweight have reduced BCM through epigenetic modifications, making them more susceptible to diabetes in the future. Similarly, in humans, we revealed that individuals born with low birthweight have lower BCM in adulthood. Because β-cell replication is more frequently observed in the 5 years after birth, and β cells are found to be more plastic in that period, a history of childhood obesity increases BCM. BCM in patients with T2DM is reduced by 20% to 65% compared with that in individuals without T2DM. However, since BCM starts to decrease from the stage of borderline diabetes, early intervention is essential for β-cell protection. In this review, we summarize the current knowledge on regulatory factors of human BCM in health and diabetes and propose the β-cell–centric concept of diabetes to enhance a more pathophysiology-based treatment approach for T2DM.

• beta-cell mass
• beta-cell regulator
• beta-cell workload
• human pancreas
• type 2 diabetes

• diabetes
• dipeptidyl peptidase-4
• medicinal plants
• natural compounds

• 2020R1A6A1A03044512 National Research Foundation of Korea
• NRF-2021R1A2C2004177 National Research Foundation of Korea
• NRF-2019R1C1C1006542 National Research Foundation of Korea

• DPP-4 inhibitors
• Immunomodulation
• Immunotherapy
• LADA
• Type 1 diabetes
• VIDPP-4i
• Vitamin D

• Animals
• Diabetes Mellitus, Type 1/drug therapy
• Diabetes Mellitus, Type 1/immunology
• Dipeptidyl-Peptidase IV Inhibitors/pharmacology
• Dipeptidyl-Peptidase IV Inhibitors/therapeutic use
• Drug Combinations
• Humans
• Immunomodulation
• Vitamin D/pharmacology
• Vitamin D/therapeutic use
• Vitamins/pharmacology
• Vitamins/therapeutic use

• Fotagliptin benzoate
• drug-drug interaction
• pharmacokinetics
• safety
• type 2 diabetes mellitus

• fotagliptin benzoate, pharmacodynamics, pharmacokinetics, safety
• type 2 diabetes mellitus

• glycaemic control
• systematic review
• weight control

• Blood Glucose
• Body Weight
• Diabetes Mellitus, Type 2/drug therapy
• Diabetes Mellitus, Type 2/epidemiology
• Dipeptidyl-Peptidase IV Inhibitors/therapeutic use
• Drug Therapy, Combination
• Glycated Hemoglobin/analysis
• Glycemic Control
• Humans
• Hypoglycemic Agents/therapeutic use
• Metformin/therapeutic use
• Observational Studies as Topic
• Sodium-Glucose Transporter 2 Inhibitors/therapeutic use

Previous studies showed inconsistent Results of the effects of dipeptidyl peptidase (DPP)-IV inhibitors on syngeneic mouse islet transplantation. We hypothesized that the implanted islet numbers are critical for the effects of DPP-IV inhibitors on the outcomes of transplantation.

One hundred and fifty or three hundred islets were syngeneically transplanted under the renal capsule of each streptozocin-diabetic C57BL/6 mouse and recipients were then treated without or with LAF237 (10 mg/kg/day, po) for 6 weeks. After transplantation, recipients’ blood glucose, body weight and intraperitoneal glucose tolerance test (IPGTT) were followed-up periodically. The graft was removed for the measurement of β-cell mass at 6 weeks.

In recipients with 150 islets, it was not significantly different between the LAF237- treated group (n = 14) and control group (n = 14) in terms of the blood glucose, body weight, glucose tolerance at 2, 4 and 6 weeks or the graft β-cell mass at 6 weeks. In contrast, in recipients with 300 islets, the LAF237-treated group (n = 24) did have a lower area under the curve of the IPGTT at 4 weeks (p = 0.0237) and 6 weeks (p = 0.0113) as well as more graft β-cell mass at 6 weeks (0.655 ± 0.008 mg vs. 0.435 ± 0.006 mg, p = 0.0463) than controls (n = 24).

Our findings revealed 6-week treatment of LAF237 improves glucose tolerance and increases graft β-cell mass in diabetic mice transplanted with a sufficient number but not a marginal number of islets. These indicate that the effects of DPP-IV inhibitors are influenced by the implanted islet mass.

• Adamantane/analogs & derivatives
• Animals
• Blood Glucose
• Body Weight
• Diabetes Mellitus, Experimental/drug therapy
• Diabetes Mellitus, Experimental/surgery
• Dipeptidyl-Peptidase IV Inhibitors/pharmacology
• Dipeptidyl-Peptidase IV Inhibitors/therapeutic use
• Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
• Humans
• Hypoglycemic Agents/pharmacology
• Mice
• Mice, Inbred C57BL
• Pyrrolidines

• Algorithms
• Animals
• Glucose Clamp Technique
• Humans
• Hypoglycemic Agents/pharmacokinetics
• Insulin/pharmacokinetics
• Mice
• Rats

• R01 DK040949 NIDDK NIH HHS
• JDRF

Dipeptidyl peptidase-4 (DPP-4) inhibitors have been suggested to have pancreatic beta-cell preserving effect according to studies using homeostatic model of assessment for beta-cell function (HOMA-β). However, whether HOMA-β is a suitable biomarker for comparisons between hypoglycemic drugs with different mechanisms of action remains unclear. Therefore, we conducted a meta-analysis to compare the effects of DPP-4 inhibitors and other classes of hypoglycemic drugs on HOMA-β and proinsulin-to-insulin ratio (PIR).

We searched MEDLINE, CENTRAL, and Ichushi-web for the period of 1966 to May 2020. We collected randomized, controlled clinical trials in patients with type 2 diabetes mellitus comparing DPP-4 inhibitors and other classes of hypoglycemic agents [α-glucosidase inhibitors (α-GIs), glucagon-like peptide-1 (GLP-1) analogues, metformin, sodium-glucose cotransporter 2 (SGLT2) inhibitors, sulfonylureas, or thiazolidinediones]. Weighted mean differences and 95% confidence intervals of changes in HOMA-β or PIR during study periods were calculated for pairwise comparisons.

Thirty-seven and 21 relevant trials were retrieved for comparisons of HOMA-β and PIR, respectively. HOMA-β and PIR consistently showed superiority of DPP-4 inhibitors compared with α-GIs. Both biomarkers consistently supported inferiority of DPP-4 inhibitors compared with GLP-1 analogues. However, PIR showed inferiority of DPP-4 inhibitors compared with metformin, and superiority compared with SGLT2 inhibitors, whereas HOMA-β showed no significant differences between DPP-4 inhibitors and the two other agents.

DPP-4 inhibitors appear to be superior to α-GIs but inferior to GLP-1 analogues in preservation of beta-cell function assessed by either HOMA-β or PIR. DPP-4 inhibitors seem to be superior to SGLT2 inhibitors but inferior to metformin on islet function assessed only by PIR. Because HOMA-β and PIR may indicate different aspects of beta-cell function, results of beta-cell function preserving effects of hypoglycemic agents should be interpreted with caution.

• Cluster of differentiation 26
• Dipeptidyl peptidase 4
• Immunotherapy
• Type 2 diabetes mellitus

• Animals
• Diabetes Mellitus, Type 2/drug therapy
• Diabetes Mellitus, Type 2/immunology
• Dipeptidyl Peptidase 4/immunology
• Dipeptidyl-Peptidase IV Inhibitors/administration & dosage
• Dipeptidyl-Peptidase IV Inhibitors/immunology
• Humans
• Immunologic Factors/administration & dosage
• Immunologic Factors/immunology
• Immunotherapy/methods
• Immunotherapy/trends
• T-Lymphocytes/drug effects
• T-Lymphocytes/immunology

• Latent autoimmune diabetes in adults
• autoimmune
• diabetes mellitus
• β cell

• Adult
• Age of Onset
• Autoantibodies/immunology
• Autoimmunity/immunology
• Diabetes Mellitus, Type 1/epidemiology
• Diabetes Mellitus, Type 1/immunology
• Humans

• DPP-4 inhibitor
• GLP-1
• experimental type 1 diabetes
• regulatory T cells
• sitaglipitin

• Dipeptidyl peptidase 4
• Inflammatory bowel disease
• Multiple sclerosis
• Rheumatoid arthritis
• Systemic lupus erythematosus
• Type 1 diabetes

• Animals
• Autoimmune Diseases/immunology
• Dipeptidyl Peptidase 4/immunology
• Humans

The study shows that treatment of NOD mice with either of two tellurium-based small molecules, AS101 [ammonium trichloro(dioxoethylene-o,o')tellurate] or SAS [octa-O-bis-(R,R)-tartarate ditellurane] could preserve β cells function and mass. These beneficial effects were reflected in decreased incidence of diabetes, improved glucose clearance, preservation of body weight, and increased survival. The normal glucose levels were associated with increased insulin levels, preservation of β cell mass and increased islet size. Importantly, this protective activity could be demonstrated when the compounds were administered either at the early pre-diabetic phase with no or initial insulitis, at the pre-diabetic stage with advanced insulitis, or even at the advanced, overtly diabetic stage. We further demonstrate that both tellurium compounds prevent migration of autoimmune lymphocytes to the pancreas, via inhibition of the α4β7 integrin activity. Indeed, the decreased migration resulted in diminished pancreatic islets damage both with respect to their size, β cell function, and caspase-3 activity, the hallmark of apoptosis. Most importantly, AS101 and SAS significantly elevated the number of T regulatory cells in the pancreas, thus potentially controlling the autoimmune process. We show that the compounds inhibit pancreatic caspase-1 activity followed by decreased levels of the inflammatory cytokines IL-1β and IL-17 in the pancreas. These properties enable the compounds to increase the proportion of Tregs in the pancreatic lymph nodes. AS101 and SAS have been previously shown to regulate specific integrins through a unique redox mechanism. Our current results suggest that amelioration of disease in NOD mice by this unique mechanism is due to decreased infiltration of pancreatic islets combined with increased immune regulation, leading to decreased inflammation within the islets. As these tellurium compounds show remarkable lack of toxicity in clinical trials (AS101) and pre-clinical studies (SAS), they may be suitable for the treatment of type-1 diabetes.

• IL-1β
• Tregs
• diabetes
• inflammation
• integrin
• tellurium

• Apoptosis
• DDR-1
• DPP4 inhibitor
• Neonatal-STZ diabetes
• β cell regeneration

• Antidiabetic agents
• Dipeptidyl-peptidase 4 inhibitors
• Insulin resistance
• Thiazolidinedione
• β-Cell function

Dipeptidyl peptidase IV (DPP-IV) inhibitors occupy a growing place in the drugs used for the management of type 2 diabetes. Recently, food components, including food-derived bioactive peptides, have been suggested as sources of DPP-IV inhibitors without side effects. Chinese black tea is a traditional health beverage, and it was used for finding DPP-IV inhibitory peptides in this study. The ultra-filtrated fractions isolated from the aqueous extracts of black tea revealed DPP-IV inhibitory activity in vitro. Four peptides under 1 kDa were identified by SDS-PAGE and LC-MS/MS (Liquid Chromatography-Mass Spectrometry-Mass Spectrometry) from the ultra-filtrate. The peptide II (sequence: AGFAGDDAPR), with a molecular mass of 976 Da, showed the greatest DPP-IV inhibitory activity (in vitro) among the four peptides. After administration of peptide II (400 mg/day) for 57 days to streptozotocin (STZ)-induced hyperglycemic mice, the concentration of glucagon-like peptide-1 (GLP-1) in the blood increased from 9.85 ± 1.96 pmol/L to 19.22 ± 6.79 pmol/L, and the insulin level was increased 4.3-fold compared to that in STZ control mice. Immunohistochemistry revealed the improved function of pancreatic beta-cells and suppressed proliferation of pancreatic alpha-cells. This study provides new insight into the use of black tea as a potential resource of food-derived DPP-IV inhibitory peptides for the management of type 2 diabetes.

• GLP-1
• dipeptidyl peptidase IV inhibitor
• peptide
• streptozotocin
• tea
• type 2 diabetes

• Adiponectin
• Diabetes mellitus
• Oxidative stress
• Pancreatic islets
• Quercetin
• Sitagliptin

Type 1 diabetes is caused by destruction of beta cells of pancreas. Vildagliptin (VG), a dipeptidyl peptidase IV (DPP IV) inhibitor, is an anti-diabetic drug, which increases beta cell mass. In the present study, the effects of VG on generation of insulin-producing cells (IPCs) from adipose-derived mesenchymal stem cells (ASCs) is investigated.

In this experimental study, ASCs were isolated and after characterization were exposed to differentiation media with or without VG. The presence of IPCs was confirmed by morphological analysis and gene expression (Pdx-1, Glut-2 and Insulin). Newport Green staining was used to determine insulin-positive cells. Insulin secretion under different concentrations of glucose was measured using radioimmunoassay method.

In the presence of VG the morphology of differentiated cells was similar to the pancreatic islet cells. Expression of Pdx-1, Glut-2 and Insulin genes in VG-treated cells was significantly higher than the cells exposed to induction media only. Insulin release from VG-treated ASCs showed a nearly 3.6 fold (P<0.05) increase when exposed to a high- glucose medium in comparison to untreated ASCs. The percentage of insulin-positive cells in the VG-treated cells was approximately 2.9-fold higher than the untreated ASCs.

The present study has demonstrated that VG elevates differentiation of ASCs into IPCs. Improvement of this protocol may be used in cell therapy in diabetic patients.

• Adipose Tissue
• Insulin-Secreting Cells
• Mesenchymal Stem Cells

• dipeptidyl peptidase-4 inhibitors
• glycaemic durability
• glycated haemoglobin
• meta-analysis
• sulphonylureas

• Blood Glucose/drug effects
• Blood Glucose/metabolism
• Diabetes Mellitus, Type 2/blood
• Diabetes Mellitus, Type 2/drug therapy
• Diabetes Mellitus, Type 2/epidemiology
• Dipeptidyl-Peptidase IV Inhibitors/therapeutic use
• Female
• Glycated Hemoglobin/drug effects
• Glycated Hemoglobin/metabolism
• Humans
• Hypoglycemic Agents/therapeutic use
• Male
• Middle Aged
• Randomized Controlled Trials as Topic/statistics & numerical data
• Sulfonylurea Compounds/therapeutic use
• Time Factors

• Blood Glucose/drug effects
• Blood Glucose/metabolism
• Clinical Trials as Topic/statistics & numerical data
• Diabetes Mellitus, Type 1/blood
• Diabetes Mellitus, Type 1/drug therapy
• Diabetes Mellitus, Type 1/epidemiology
• Dipeptidyl-Peptidase IV Inhibitors/therapeutic use
• Glycated Hemoglobin/metabolism
• Humans
• Hypoglycemic Agents/therapeutic use
• Insulin/therapeutic use
• Postprandial Period

• Diabetes Mellitus, Type 2/drug therapy
• Exenatide
• Glucagon/analogs & derivatives
• Glucagon/physiology
• Glucagon/therapeutic use
• Glucagon-Like Peptide 1
• Humans
• Hypoglycemic Agents/therapeutic use
• Liraglutide
• Peptide Fragments/physiology
• Peptides/therapeutic use
• Protein Precursors/physiology
• Venoms/therapeutic use

• Antibody
• Epitope
• NOD mice
• Type 1 diabetes
• Vaccine

• Diabetes mellitus
• Glutamine
• Insulin
• Rat
• SNAT2

• bariatric surgery
• diabetes
• incretins
• peptide tyrosine tyrosine (PYY)

• Animals
• Bariatric Surgery
• Diabetes Mellitus, Type 2/metabolism
• Diabetes Mellitus, Type 2/physiopathology
• Diabetes Mellitus, Type 2/surgery
• Gastrointestinal Hormones/physiology
• Glucose/metabolism
• Homeostasis
• Humans
• Islets of Langerhans/physiology
• Peptide YY/physiology

• Animals
• Cell Count
• Cell Proliferation/drug effects
• Diabetes Mellitus, Type 2/drug therapy
• Diabetes Mellitus, Type 2/pathology
• Diet, Fat-Restricted
• Diet, High-Fat
• Exenatide
• Hypoglycemic Agents/therapeutic use
• Incretins/therapeutic use
• Insulin-Secreting Cells/drug effects
• Insulin-Secreting Cells/pathology
• Insulin-Secreting Cells/physiology
• Male
• Mice
• Mice, Inbred C57BL
• Pancreas/drug effects
• Pancreas/pathology
• Peptides/therapeutic use
• Sitagliptin Phosphate/therapeutic use
• Venoms/therapeutic use

• P30 CA125123 NCI NIH HHS
• P30 DK079638 NIDDK NIH HHS
• R01 AG040110 NIA NIH HHS