Insulin increases H2O2-induced pancreatic beta cell death

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

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


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 H2O 2-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 poptosis.

Original languageEnglish
Pages (from-to)1165-1176
Number of pages12
JournalApoptosis : an international journal on programmed cell death
Issue number10
StatePublished - Oct 2010


  • Apoptosis
  • Beta cell death
  • IR signaling
  • Oxidative stress
  • ROS


Dive into the research topics of 'Insulin increases H2O2-induced pancreatic beta cell death'. Together they form a unique fingerprint.

Cite this