Overexpression of IRS2 in isolated pancreatic islets causes proliferation and protects human [beta]-cells from hyperglycemia-induced apoptosis.
Mohanty, S. a; Spinas, G. A. a; Maedler, K. a; Zuellig, R. A. a; Lehmann, R. a; Donath, M. Y. a; Trub, T. b; Niessen, M. a,*
[Article] Experimental Cell Research. 303(1):68-78, February 2005.

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Studies in vivo indicate that IRS2 plays an important role in maintaining functional [beta]-cell mass. To investigate if IRS2 autonomously affects [beta]-cells, we have studied proliferation, apoptosis, and [beta]-cell function in isolated rat and human islets after overexpression of IRS2 or IRS1. We found that [beta]-cell proliferation was significantly increased in rat islets overexpressing IRS2 while IRS1 was less effective. Moreover, proliferation of a [beta]-cell line, INS-1, was decreased after repression of Irs2 expression using RNA oligonucleotides. Overexpression of IRS2 in human islets significantly decreased apoptosis of [beta]-cells, induced by 33.3 mM d-glucose. However, IRS2 did not protect cultured rat islets against apoptosis in the presence of 0.5 mM palmitic acid. Overexpression of IRS2 in isolated rat islets significantly increased basal and d-glucose-stimulated insulin secretion as determined in perifusion experiments. Therefore, IRS2 is sufficient to induce proliferation in rat islets and to protect human [beta]-cells from d-glucose-induced apoptosis. In addition, IRS2 can improve [beta]-cell function. Our results indicate that IRS2 acts autonomously in [beta]-cells in maintenance and expansion of functional [beta]-cell mass in vivo.

(C) 2005Elsevier, Inc.