title: Visfatin inhibits apoptosis of pancreatic β-cell line, MIN6, via the mitogen-activated protein kinase/phosphoinositide 3-kinase pathway.
abstract: Visfatin is an adipocytokine that plays an important role in attenuating insulin resistance by binding to insulin receptor. It has been suggested that visfatin plays a role in the regulation of cell apoptosis and inflammation by an as yet unidentified mechanism. This study investigated the protective effects of visfatin on palmitate-induced islet β-cell apoptosis in the clonal mouse pancreatic β-cell line MIN6. The cells were treated with palmitate and/or recombinant visfatin. An 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan assay was used to detect cell proliferation, V-FITC/propidium iodide staining was used to measure cell apoptosis and necrosis, and western blot analysis was used to detect the expression of proapoptotic proteins. The incubation of the cells with visfatin led to a concentration-dependent increase of cell proliferation (1.55-fold at 10(-7) M and 24 h compared with control, P<0.05). Visfatin significantly reduced the cell apoptosis induced by palmitate and caused a significant change in the expression of several proapoptotic proteins, including upregulation of Bcl-2 and a marked downregulation of cytochrome c and caspase 3. Visfatin also activated the ERK1/2 and the phosphoinositide 3-kinase (PI3K)/AKT signaling pathways in a time- and concentration-dependent manner, and the effect of visfatin on apoptosis was blocked by the specific ERK1/2 and PI3K/AKT inhibitors, PD098059 and LY294002. We conclude that visfatin can increase β-cell proliferation and prevent apoptosis, activate intracellular signaling, and regulate the expression of proapoptotic proteins. The antiapoptotic action of visfatin is mediated by activation of mitogen-activated protein kinase-dependent and PI3K-dependent signaling pathways.
authors.affiliation: Diabetes Research Laboratory, Department of Endocrinology and Metabolism, Shanghai Jiaotong University Affiliated First People's Hospital, 100 Hainin Road, Shanghai 200080, People's Republic of China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Cheng
authors.forename: Weipin
authors.initials: W
authors.lastname: Dong
authors.forename: Lei
authors.initials: L
authors.lastname: Qian
authors.forename: Jingcheng
authors.initials: J
authors.lastname: Wu
authors.forename: Yongde
authors.initials: Y
authors.lastname: Peng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D054409:Nicotinamide Phosphoribosyltransferase / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009765:Obesity / Q000503:physiopathology; D019308:Palmitic Acid / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D053148:Caspase 3; D002867:Chromones; D045304:Cytochromes c; D005419:Flavonoids; D020928:Mitogen-Activated Protein Kinases; D009025:Morpholines; D054409:Nicotinamide Phosphoribosyltransferase; D019308:Palmitic Acid; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one