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Resistin induces rat insulinoma cell RINm5F apoptosis

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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.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (No 30371502; 30571978), the Natural Science Foundation of Jiangsu Province (No BK2001120), and a grant from Jiangsu Province Health Department (No RC2002061).

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Authors and Affiliations

  1. Department of Pediatrics, Nanjing Maternity & Child Health Hospital of Nanjing Medical University, Nanjing, 210004, China

    Chun-lin Gao, Xiao-hui Chen & Xi-rong Guo

  2. Institute of Pediatrics of Nanjing Medical University, Nanjing, 210029, China

    Chun-lin Gao, Jie Qiu, Chun-mei Zhang, Chen-bo Ji, Xiao-hui Chen, Feng Liu & Xi-rong Guo

  3. Department of Respiratory Medicine, Nanjing Children’s Hospital Affiliated to Nanjing Medical University, Nanjing, 210029, China

    De-yu Zhao & Feng Liu

Authors
  1. Chun-lin Gao
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  2. De-yu Zhao
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  3. Jie Qiu
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  4. Chun-mei Zhang
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  7. Feng Liu
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Correspondence to Feng Liu or Xi-rong Guo.

Additional information

C.-l. Gao and D.-y. Zhao contributed equally to this work.

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Gao, Cl., Zhao, Dy., Qiu, J. et al. Resistin induces rat insulinoma cell RINm5F apoptosis. Mol Biol Rep 36, 1703–1708 (2009). https://doi.org/10.1007/s11033-008-9371-8

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  • DOI: https://doi.org/10.1007/s11033-008-9371-8

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