期刊
JOURNAL OF DIABETES AND ITS COMPLICATIONS
卷 26, 期 4, 页码 266-274出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jdiacomp.2012.03.013
关键词
Dipeptidyl peptidase-IV; Glucagon like peptide-1; Insulin; beta-cell regeneration; beta-cell apoptosis; Diabetes
资金
- Govt. of NCF Delhi, India
Objective: Inhibitors of dipeptidyl peptidase-4 (DPP-4), a key regulator of the actions of incretin hormones, exert antihyperglycemic effects in type 2 diabetic patients. A major unanswered question concerns the potential ability of DPP-4 inhibition to have beneficial disease-modifying effects, specifically to attenuate loss of pancreatic beta-cell mass and function due to oxidative stress induced inflammation. Here, we investigated the effects of a potent and selective DPP-4 inhibitor vildagliptin on glycemic control, pancreatic beta-cell mass and function, genes and proteins expressions, tumor necrosis factor-alpha, and nitric oxide in an n2-STZ diabetic model of rat with defects in insulin sensitivity and secretion. Method: To induce NIDDM, STZ (sigma chemicals, USA) (90 mg/kg) was administered i.p. to a group of 2 days old pups. Another group of pups received only saline. The pups were weaned for 21 days, and 6 weeks after the injection of STZ, the animals were checked for fasting glucose level (FPG) >= 160 mg/dl were considered as diabetic. Results: Significant and dose-dependent correction of postprandial and fasting hyperglycemia was observed in diabetic rats following 8 weeks of chronic therapy. Treatment with vildagliptin showed increase in the number of insulin-positive beta-cells in islets and improved the expressions of genes and proteins are responsible for insulin secretions. In addition, treatment of rats with vildagliptin significantly increased insulin content; and decreased the nitric oxide and TNF-alpha concentration. Conclusion: These findings suggest that DPP-4 inhibitors may offer long-lasting efficacy in the treatment of diabetes mellitus by modifying the courses of the disease. (C) 2012 Elsevier Inc. All rights reserved.
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