Reversal of New-Onset Diabetes through Modulating Inflammation and Stimulating β-Cell Replication in Nonobese Diabetic Mice by a Dipeptidyl Peptidase IV Inhibitor

Liu, Tian; Gao, Jie; Hao, Jingbin; Yi, Huimin; O’Brien, Timothy; Sorenson, Robert L.; Zhang, Guo

doi:10.1210/jcem.95.6.9988

Cited by 23 publications

(45 citation statements)

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“…This effect has been attributed to the inhibition of CD26 (DPP4) and modulation of T cell migration [33,36,40]. However, we did not observe significant effects of DPP4 inhibition in the model of established type 1 diabetes.…”

Section: Discussioncontrasting

confidence: 57%

“…However, safety issues such as teratoma formation and low reprogramming efficiency preclude clinical application of iPS-derived beta cell technology. Other methods increasing compromised beta cell mass comprise diverse pharmacological agents or hormones, including GLP-1 and DPP4 inhibitors [29][30][31][32][33][34][35][36]. In mice treated with Pam3CSK 4 +DA-1229, a beta cell-trophic effect of DPP4 inhibition was demonstrated by increased numbers of proliferating beta cells and small beta cell units.…”

Section: Discussionmentioning

confidence: 99%

“…It was reported that DPP4 inhibitors, even without immune modulators, could reverse new-onset diabetes of NOD mice [36]. This effect has been attributed to the inhibition of CD26 (DPP4) and modulation of T cell migration [33,36,40].…”

Section: Discussionmentioning

confidence: 99%

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Treatment of autoimmune diabetes in NOD mice by Toll-like receptor 2 tolerance in conjunction with dipeptidyl peptidase 4 inhibition

Kim

Lee

et al. 2012

Diabetologia

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Aims/hypothesis We have shown that chronic administration of the Toll-like receptor 2 (TLR2) agonist Pam3CSK 4 prevents diabetes in NOD mice by inducing TLR2 tolerance of dendritic cells (DCs). We have also reported that a novel dipeptidyl peptidase 4 (DPP4) inhibitor, DA-1229, could increase beta cell mass. Here we investigated whether a combination of DPP4 inhibition, with beneficial effects on beta cell mass, and TLR2 tolerisation, protecting beta cells from autoimmune destruction, could treat a model of established type 1 diabetes. Methods Diabetic NOD mice were treated with 100 μg Pam3CSK 4 , administered three times a week for 3 weeks, in combination with feeding with chow containing 0.3% DA-1229. Beta cell mass and proliferation were studied by immunohistochemistry. DC tolerance was assessed by studying diabetogenic CD4 + T cell priming after adoptive transfer and expression of costimulatory molecules on DCs by flow cytometry. Results

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Section: Discussioncontrasting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

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Treatment of autoimmune diabetes in NOD mice by Toll-like receptor 2 tolerance in conjunction with dipeptidyl peptidase 4 inhibition

Kim

Lee

et al. 2012

Diabetologia

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“…Existing studies indicate that DPP-4 inhibitors have the potential to protect β-cell function [11,12] in persons with T2DM as well as in a mouse model of AI diabetes [15] which indicates the possible role of DPP-4 activity in the disease pathogenesis . Our present results are consistent with that hypothesis especially because LADA might represent the combination of underlying risk factors of both types of diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…DPP-4 inhibition reduces insulitis as well, and stimulates β -cell function in a non-obese diabetic mouse model of AI diabetes, a classic model of T1DM [13,14]. There is an increased serum DPP-4 activity [15] and expression on terminally differentiated CD4 T-cells [16] in persons with T1DM. Recent trials show that one of the DPP-4 inhibitors, sitagliptin, significantly improves glycaemic control in adult persons with T1DM [17] as well as in persons with LADA [18].…”

Section: Introductionmentioning

confidence: 99%

Persons with latent autoimmune diabetes in adults express higher dipeptidyl peptidase-4 activity compared to persons with type 2 and type 1 diabetes

Duvnjak

Blaslov

Lovrenčić

et al. 2016

Diabetes Research and Clinical Practice

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Combination of Vildagliptin and Pioglitazone in Experimental Type 2 Diabetes in Male Rats

Refaat

Sakr

Salama

et al. 2016

Drug Development Research

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Preclinical Research The majority of studies on vildagliptin and pioglitazone have focused on their combination in glycemic control. The aim of the present study was to investigate their effects in combination on (i) hyperglycemia-induced oxidative stress and inflammation and (ii) on organs involved in the pathophysiology of diabetes, pancreas, kidney and liver. Type 2 diabetes was induced using low-dose streptozotocin in male Wistar rats. Diabetic rats were treated for 4 weeks, with vildagliptin (10 mg/kg/day), pioglitazone (10 mg/kg/day) and their combination. Diabetic rats showed elevated fasting serum glucose, fasting serum insulin, serum transaminases together with a deleterious lipid profile and elevated serum creatinine and urea concentrations. Serum levels of the inflammatory markers tumor necrosis factor-α (TNF-α) and nitrite/nitrate were also elevated compared to normal rats. Oxidative stress was manifested by lowered hepatic reduced glutathione (GSH) and increased malondialdehyde (MDA) levels. Pancreatic sections from diabetic rats showed degenerated islets with poorly maintained architecture that was prevented by drug treatment. Pioglitazone was generally more effective than vildagliptin in the studied parameters except for the lipid profile where the effect of both drugs was comparable and for the liver enzymes and renal parameters where vildagliptin was more effective. The combination of vildagliptin and pioglitazone produced superior effects than either drug alone. Drug Dev Res 77 : 251-257, 2016. © 2016 Wiley Periodicals, Inc.

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Reversal of New-Onset Diabetes through Modulating Inflammation and Stimulating β-Cell Replication in Nonobese Diabetic Mice by a Dipeptidyl Peptidase IV Inhibitor

Cited by 23 publications

References 0 publications

Treatment of autoimmune diabetes in NOD mice by Toll-like receptor 2 tolerance in conjunction with dipeptidyl peptidase 4 inhibition

Treatment of autoimmune diabetes in NOD mice by Toll-like receptor 2 tolerance in conjunction with dipeptidyl peptidase 4 inhibition

Persons with latent autoimmune diabetes in adults express higher dipeptidyl peptidase-4 activity compared to persons with type 2 and type 1 diabetes

Combination of Vildagliptin and Pioglitazone in Experimental Type 2 Diabetes in Male Rats

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