Dipeptidyl peptidase-4 inhibitor impacts the expression of Bcl-2 and Bax through γ amino acid bwtyric acid in pancreas islets

Objective To explore the effects of dipeptidyl peptidase(DPP-4)inhibitor on proteins expression of Bcl-2 and Bax of islet β-cells through increasing the expression of islet γ amino acid butyric acid(GABA). Methods A total of 50 rats of clean grade were studied. Among them, ten rats were randomly selected as normal controls, the remaining forty rats were fed with high-fat diet and then intraperitoneal injection with streptozotocin, the diabetic rats models were then established. Rats were randomly divided into three groups: i.e. diabetic control group, DPP-4 inhibitor group, and antagonist group(DPP-4 inhibitor and GABA receptor antagonist). Six weeks later, blood glucose, serum insulin, glucagon, and the proteins expression of GABA, Bcl-2, and Bax of islet β-cells were measured. Results (1)Compared with diabetic control group, serum insulin was increased(P<0.05), blood glucose and serum glucagon were decreased in DPP-4 inhibitor group(P<0.05). (2)Compared with DPP-4 inhibitor group, serum insulin was decreased(P<0.05), blood glucose and serum glucagon were increased(P<0.05)in antagonist group.(3)Compared with diabetic control group, the expression of GABA was increased(P<0.05), the expression of Bcl-2 protein was increased(P<0.05)in pancreatic β-cells in DPP-4 inhibitor group.(4)Compared with diabetic control group, the expression of GABA in pancreatic β-cells was increased in antagonist group(P<0.05). Compared with DPP-4 inhibitor group, the expression of Bax protein in pancreatic β-cells was increased in antagonist group(P<0.05), while the expression of Bcl-2 protein was decreased(P<0.05). Conclusions DPP-4 inhibitor could increase the secretion of insulin, decrease the secretion of glucagon, up-regulate expression of anti-apoptosis protein Bcl-2, and down-regulate expression of apoptosis protein Bax in pancreatic β-cells through increasing the expression of GABA, inhibiting pancreatic β-cells apoptosis and protecting the damaged β-cells in type 2 diabetic rats. (Chin J Endocrinol Metab, 2016, 32: 227-231) Key words: Dipeptidyl peptidase-4 inhibitor; γ amino acid butyric acid; Bcl-2 protein; Bax protein; Islet β -cell apoptosis