Tissue inhibitor of metalloproteinase-1 counteracts glucolipotoxicity in the pancreatic β-cell line INS-1  

作　　者：JIANG Hong-wei ZHU Han-yu WANG Jian-zhong FU Bo LU Yang HONG Quan XIE Yuan-sheng CHEN Xiang-mei 

机构地区：[1]Institute of Nephrology, General Hospital of Chinese People's Liberation Army, Beijing 100853, China [2]Department of Endocrinology and Metabolism, First Affiliated Hospital, Henan University of Science and Technology, Luoyang, Henan 471003, China

出　　处：《Chinese Medical Journal》2011年第2期258-261,共4页中华医学杂志（英文版）

摘　　要：Background Glucolipotoxicity might play an important role in the β cell decompensation stage during the development of obesity-associated type 2 diabetes.Tissue inhibitor of metalloproteinase-1 （TIMP-1） inhibits matrix metalloproteinase （MMP） activity and regulates proliferation and apoptosis of a variety of cell types,including pancreatic β-cells.In the present study,we investigated whether TIMP-1 counteracts glucolipotoxicity in the pancreatic β-cell line INS-1.Methods INS-1 cells were incubated in normal or high glucose,with or without palmitate （0.4 mmol/L）,in the presence of TIMP-1 or MMP inhibitor GM60001.In some experiments,cells were pretreated with phosphatidylinositol-3 （Pl-3） kinase inhibitor,LY294002 or wortmannin.The amount of dead INS-1 cells was determined by HO342 and propidium iodide staining.Akt phosphorylation was evaluated by Western blotting analysis to investigate a possible mechanism of TIMP-1＇s action.Results TIMP-1 protected INS-1 cells from glucolipotoxicity independent of MMP inhibition.TIMP-1 stimulated Akt phosphorylation.Inhibition of the PI-3 kinase pathway abolished the survival effect of TIMP-1.Conclusion TIMP-1 may counteract glucolipotoxicity induced β-cell death via a PI-3 kinase pathway.Background Glucolipotoxicity might play an important role in the β cell decompensation stage during the development of obesity-associated type 2 diabetes.Tissue inhibitor of metalloproteinase-1 （TIMP-1） inhibits matrix metalloproteinase （MMP） activity and regulates proliferation and apoptosis of a variety of cell types,including pancreatic β-cells.In the present study,we investigated whether TIMP-1 counteracts glucolipotoxicity in the pancreatic β-cell line INS-1.Methods INS-1 cells were incubated in normal or high glucose,with or without palmitate （0.4 mmol/L）,in the presence of TIMP-1 or MMP inhibitor GM60001.In some experiments,cells were pretreated with phosphatidylinositol-3 （Pl-3） kinase inhibitor,LY294002 or wortmannin.The amount of dead INS-1 cells was determined by HO342 and propidium iodide staining.Akt phosphorylation was evaluated by Western blotting analysis to investigate a possible mechanism of TIMP-1＇s action.Results TIMP-1 protected INS-1 cells from glucolipotoxicity independent of MMP inhibition.TIMP-1 stimulated Akt phosphorylation.Inhibition of the PI-3 kinase pathway abolished the survival effect of TIMP-1.Conclusion TIMP-1 may counteract glucolipotoxicity induced β-cell death via a PI-3 kinase pathway.

关 键 词：GLUCOLIPOTOXICITY tissue inhibitor of metalloproteinase-1 pancreatic β-cell line INS-1 

分 类 号：TQ[化学工程]