title: Insulin increases H2O2-induced pancreatic beta cell death.
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 H(2)O(2), 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 H(2)O(2) 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 H(2)O(2)-induced cell death. Insulin increased ROS production by pancreatic β cells and increased the effect of H(2)O(2). 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 H(2)O(2) and, perhaps, other inducers of apoptosis.
authors.affiliation: Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel. ssampson@013.net
authors.forename: S R
authors.initials: SR
authors.lastname: Sampson
authors.forename: E
authors.initials: E
authors.lastname: Bucris
authors.forename: M
authors.initials: M
authors.lastname: Horovitz-Fried
authors.forename: A
authors.initials: A
authors.lastname: Parnas
authors.forename: S
authors.initials: S
authors.lastname: Kahana
authors.forename: G
authors.initials: G
authors.lastname: Abitbol
authors.forename: M
authors.initials: M
authors.lastname: Chetboun
authors.forename: T
authors.initials: T
authors.lastname: Rosenzweig
authors.forename: C
authors.initials: C
authors.lastname: Brodie
authors.forename: S
authors.initials: S
authors.lastname: Frankel
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D018384:Oxidative Stress; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D007328:Insulin; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D020169:Caspases