The influence of novel GPR119 agonist on body weight, food intake and glucose metabolism in obesity rats provoked high-fat and -carbohydrate diet

Abstract

The search for new drugs for the treatment of type 2 diabetes mellitus (T2DM) and obesity remains an urgent problem. Drugs with influence on incretin system are widely used in the treatment of T2DM and obesity, since in addition to the hypoglycemic action of their inherent hypophagic effects. With the discovery of GPR119 receptor, there is the opportunity to pharmacological stimulation of endogenous secretion of incretins. Compound ZB-16 is active GPR119 agonist with IC50=7 nM. Its activation leads to increased secretion of the major incretins (GLP-1 and GIP), which are able to influence glucose metabolism and feeding behavior.Aims — to study the effect of GPR 119 receptor agonist compounds ZB-16 on blood glucose, body weight and food intake in rats with obesity.Material and methods.Male rats with initial weight 390—400 g were fed with high-carbohydrate and high-fat diet. During the next four weeks the animals orally received ZB-16 (1 mg/kg) and metformin (400 mg/kg) and then we assessed the level of water and food consumption, blood glucose levels, and performed oral glucose tolerance test (OGTT).Results.Compound ZB-16 and metformin reduced fasting blood glucose levels and weight of experimental animals, while the control rats gained weight. GPR119 agonist is more pronounced than metformin reduced the area under the curve «glucose of concentration—time» during the OGTT.Conclusions.Novel GPR119 agonist — ZB-16 is comparable to metformin in hypoglycemic and anorexigenic effect in animals with obesity caused high-carbohydrate and high-fat diet.