首页|期刊导航|中华医学杂志(英文版)|Tissue inhibitor of metalloproteinase-1 counteracts glucolipotoxicity in the pancreatic β-cell line INS-1
中华医学杂志(英文版)2011,Vol.124Issue(2):258-261,4.DOI:10.3760/cma.j.issn.0366-6999.2011.02.020
Tissue inhibitor of metalloproteinase-1 counteracts glucolipotoxicity in the pancreatic β-cell line INS-1
Tissue inhibitor of metalloproteinase-1 counteracts glucolipotoxicity in the pancreatic β-cell line INS-1
摘要
Abstract
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-1Key words
glucolipotoxicity/tissue inhibitor of metalloproteinase-1/pancreatic β-cell line INS-1引用本文复制引用
JIANG Hong-wei,ZHU Han-yu,WANG Jian-zhong,FU Bo,L(U) Yang,HONG Quan,XIE Yuan-sheng,CHEN Xiang-mei..Tissue inhibitor of metalloproteinase-1 counteracts glucolipotoxicity in the pancreatic β-cell line INS-1[J].中华医学杂志(英文版),2011,124(2):258-261,4.基金项目
This study was supported by grants from the National Basic Research Program(973 program)of China(No.2007CB507400 and 2006CB503905),the National High Technology Research and Development Program(863 Program)of China(No.2006AA02A112),the Young Scientists Fund of Henan University of Science and Technology (No.13760020). (973 program)