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Insulin increases H2O2-induced pancreatic beta cell death

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Abstract

Insulin resistance results, in part, from impaired insulin signaling in insulin target tissues. Consequently, increased levels of insulin are necessary to control plasma glucose levels. The effects of elevated insulin levels on pancreatic beta (β) cell function, however, are unclear. In this study, we investigated the possibility that insulin may influence survival of pancreatic β cells. Studies were conducted on RINm, RINm5F and Min-6 pancreatic β-cells. Cell death was induced by treatment with H2O2, and was estimated by measurements of LDH levels, viability assay (Cell-Titer Blue), propidium iodide staining and FACS analysis, and mitochondrial membrane potential (JC-1). In addition, levels of cleaved caspase-3 and caspase activity were determined. Treatment with H2O2 increased cell death; this effect was increased by simultaneous treatment of cells with insulin. Insulin treatment alone caused a slight increase in cell death. Inhibition of caspase-3 reduced the effect of insulin to increase H2O2-induced cell death. Insulin increased ROS production by pancreatic β cells and increased the effect of H2O2. These effects were increased by inhibition of IR signaling, indicative of an effect independent of the IR cascade. We conclude that elevated levels of insulin may act to exacerbate cell death induced by H2O2 and, perhaps, other inducers of apoptosis.

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Abbreviations

ROS:

Reactive oxygen species

T1DM:

Type 1 diabetes mellitus

T2DM:

Type 2 diabetes mellitus

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Acknowledgments

Supported in part by the Russell Berrie Foundation and D-Cure, Diabetes Care in Israel. SF and EB contributed equally to this study.

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Authors and Affiliations

  1. Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel

    S. R. Sampson, E. Bucris, M. Horovitz-Fried, A. Parnas, S. Kahana, G. Abitbol, M. Chetboun, C. Brodie & S. Frankel

  2. Department of Molecular Biology, Weizmann Institute of Science, Rehovot, Israel

    S. R. Sampson & E. Bucris

  3. Department of Molecular Biology, The University Center, College of Judea and Samaria, Ariel, Israel

    G. Abitbol, M. Chetboun & T. Rosenzweig

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  1. S. R. Sampson
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  2. E. Bucris
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Correspondence to S. R. Sampson.

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Sampson, S.R., Bucris, E., Horovitz-Fried, M. et al. Insulin increases H2O2-induced pancreatic beta cell death. Apoptosis 15, 1165–1176 (2010). https://doi.org/10.1007/s10495-010-0517-5

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  • DOI: https://doi.org/10.1007/s10495-010-0517-5

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