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.