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Beta-cell apoptosis induced by adipokines may result in beta-cell dysfuction in type 2 diabetes.Resistin,anadipokine-linked obesity with type 2 diabetes, impairs glucose-stimulated insulin secretion (GSIS) in beta-cells.Presently, the effectsof resistin on rat insulinoma ceils RINm5F were examined.Treatment of RINm5F with resistin induced cell damage.Tissue Inhibitor of Metalloproteinase-1(TIMP-1) protected resistin-mediated cytotoxicity in RINm5E lncubalion with resistin up-regulated caspase-3activity and induced the formation of a DNA ladder.TIMP-1 attenuated these effects.The molecular mechanism of TIMP-1 inhibitionof resistin-mediated cytotoxicity appeared to involve Akt phosphorylation and activation of IrB-α phosphorylation.Resistin treatment suppressed Akt phosphorylation and activated IkB-α phosphorylation, which could be attenuated by TIMP-1.We conclude thatresistin can induce beta-ceil apoptosis and that resistin-related beta-cell apoptosis can be prevented by TIMP-1.