title: 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.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: L
authors.initials: L
authors.lastname: Jian
authors.forename: Y X
authors.initials: YX
authors.lastname: Su
authors.forename: H C
authors.initials: HC
authors.lastname: Deng
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014280:Triglycerides / Q000097:blood
chemical_list: D052242:Adiponectin; D014280:Triglycerides; D020169:Caspases; D005947:Glucose