Adiponectin-induced Inhibition of Intrinsic and Extrinsic Apoptotic Pathways Protects Pancreatic β-Cells Against Apoptosis

Abstract

Apoptosis is the main form of β-cell death in type 2 diabetes mellitus. There are 2 major pathways leading to apoptosis, 'intrinsic and extrinsic pathways'. Adiponectin is an adipocyte-derived hormone, which plays an important role in glucose and lipid metabolism. The main aims of this study were to investigate related apoptotic pathways in diabetes and the anti-apoptosis effects of adiponectin on pancreatic β-cell and the underlying mechanisms. Diabetic mice were generated by intraperitoneal injection of streptozotocin (STZ, 50 mg/kg/d for 5 days) and high-fat diet. Adiponectin overexpressing mice were developed by injecting lentivirus expressing mouse full length adiponectin (plenti-acdc-EGFP) through tail vein. Fourteen days after plenti-acdc-EGFP lentivirus injection, plasma adiponectin protein levels were increased 2-fold. Plasma triglyceride and glucose levels, but not total cholesterol, were significantly reduced in plenti-acdc-EGFP-treated mice. Pancreatic β-cell apoptotic numbers and the expression of caspase-8, -9, -3 in islet increased in diabetic mice, which was reversed by elevated adiponectin in plenti-acdc-EGFP-treated mice. These results suggest that both intrinsic and extrinsic apoptotic pathways have an important role in diabetic β-cell apoptosis. Adiponectin has antidiabetic and anti-apoptotic effects by regulating glucose and lipid metabolisms and inhibiting intrinsic and extrinsic apoptotic pathway in pancreatic β-cells.