Influence of novel GPR119 receptor agonist on plasma glucose and insulin level, as well as structural changes of pancreas islets in rats with experimental type 2 diabetes
2016
Background. GPR119 receptor is a promising target for novel antidiabetic drugs development because of its agonists in addition to hypoglycemic effects have cytoprotective effect on beta cells. Aim — to assess the effect of the novel GPR119 receptor agonist and sitagliptin on carbohydrate metabolism and morphological structure of the pancreas in animals with experimental type 2 diabetes. Material and methods. The study was performed in Wistar rats with streptozotocin-nicotinamide-induced diabetes. Serum insulin was determined by ELISA (Rat Insulin, (INS) ELISA Kit, 96 CSB). Immunohistochemical studies were performed using mouse monoclonal antibodies to insulin (clone 1G4, GeneTex) with determination of the absolute and relative area of immunopositive material (beta-cells) of the pancreatic islets. Results. 28-day treatment of animals with diabetes by GPR119 receptor agonist — ZB-16 (dipiaron) (1 mg/kg, per os, daily) and an inhibitor of the DPP-4 (sitagliptin) led to a reduction of fasting hyperglycemia and improve its glucose tolerance and enhance basal and stimulated insulin secretion relative to the control without treatment. Morphometric assessment of islets revealed that animals treated with the ZB-16 and sitagliptin have significantly higher absolute and relative islets area, as well as the perimeter of the insulin-positive material compared to islets of rats without treatment. Conclusion. Course administration of GPR119 receptor agonist to animals with streptozotocin-nicotinamide-induced diabetes has a pronounced antidiabetic effect consists in reducing fasting plasma glucose, improve glucose utilization, increase basal and stimulated insulin secretion, as well as increasing the area of the insulin-positive material in islets. Antidiabetic action of novel GPR119 receptor agonist, was comparable to that of sitagliptin.
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