Resistin induces rat insulinoma cell RINm5F apoptosis.
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-alpha phosphorylation. Resistin treatment suppressed Akt phosphorylation and activated IkB-alpha 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.
Gao
Chun-lin
CL
Department of Pediatrics, Nanjing Maternity & Child Health Hospital of Nanjing Medical University, Nanjing, China.
Zhao
De-yu
DY
Qiu
Jie
J
Zhang
Chun-mei
CM
Ji
Chen-bo
CB
Chen
Xiao-hui
XH
Liu
Feng
F
Guo
Xi-rong
XR
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D007340:Insulinoma / Q000201:enzymology / Q000473:pathology*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D052243:Resistin / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D052243:Resistin; D019715:Tissue Inhibitor of Metalloproteinase-1; D051028:bcl-2-Associated X Protein; D000072000:NF-KappaB Inhibitor alpha; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3