期刊
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
卷 47, 期 2, 页码 456-463出版社
ELSEVIER
DOI: 10.1016/j.ejps.2012.07.003
关键词
PKF-275-055; Glucagon like peptide-1; Insulin; TNF-alpha; Nitric oxide beta-cell regeneration
资金
- Govt. of NCT Delhi, India
Inhibitors of dipeptidyl peptidase-4 (DPP-IV), a key regulator of the actions of incretin hormones, exert antihyperglycemic effects in type 2 diabetic patients. A major question concerns the potential ability of long term DPP-IV inhibition to have beneficial disease-modifying effects, specifically to attenuate loss of pancreatic beta-cell mass due to oxidative stress induced inflammation. Here, we investigated the effects of a potent and selective DPP-4 inhibitor, an analog of vildagliptin (PKF-275-055), on glycemic control, pancreatic beta-cell mass, 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. To induce NIDDM, streptozotocin (STZ) 90 mg/kg was administered i.p. to a group of 2 days old pups. Diabetic rats were administered orally with vildagliptin analog PKF-275-055. Saline treated animals served as diabetic control. Significant and dose-dependent correction of postprandial hyperglycemia was observed in diabetic rats following 8 weeks of chronic therapy. Treatment with PKF-275-055 showed increased 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 PKF-275-055 significantly increased insulin content, glycogen content and total proteins content; and decreased the inflammatory markers i.e. nitric oxide and TNF-alpha. The present studies indicate that PKF-275-055 is a novel selective DPP-IV inhibitor having potential to reduce inflammation that might be a potential agent for type 2 diabetes. (c) 2012 Elsevier B.V. All rights reserved.
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