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Resistin induces rat insulinoma cell RINm5F apoptosis
Authors:Chun-lin Gao  De-yu Zhao  Jie Qiu  Chun-mei Zhang  Chen-bo Ji  Xiao-hui Chen  Feng Liu  Xi-rong Guo
Institution:(1) Department of Pediatrics, Nanjing Maternity & Child Health Hospital of Nanjing Medical University, Nanjing, 210004, China;(2) Institute of Pediatrics of Nanjing Medical University, Nanjing, 210029, China;(3) Department of Respiratory Medicine, Nanjing Children’s Hospital Affiliated to Nanjing Medical University, Nanjing, 210029, China
Abstract:Beta-cell apoptosis induced by adipokines may result in beta-cell dysfunction in type 2 diabetes. Resistin, an adipokine-linked obesity with type 2 diabetes, impairs glucose-stimulated insulin secretion (GSIS) in beta-cells. Presently, the effects of resistin on rat insulinoma cells RINm5F were examined. Treatment of RINm5F with resistin induced cell damage. Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) protected resistin-mediated cytotoxicity in RINm5F. Incubation with resistin up-regulated caspase-3 activity and induced the formation of a DNA ladder. TIMP-1 attenuated these effects. The molecular mechanism of TIMP-1 inhibition of resistin-mediated cytotoxicity appeared to involve Akt phosphorylation and activation of IkB-α phosphorylation. Resistin treatment suppressed Akt phosphorylation and activated IkB-α phosphorylation, which could be attenuated by TIMP-1. We conclude that resistin can induce beta-cell apoptosis and that resistin-related beta-cell apoptosis can be prevented by TIMP-1. C.-l. Gao and D.-y. Zhao contributed equally to this work.
Keywords:Resistin  TIMP-1  Beta-cell  Apoptosis
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