Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10905092 | Experimental Cell Research | 2005 | 11 Pages |
Abstract
Studies in vivo indicate that IRS2 plays an important role in maintaining functional β-cell mass. To investigate if IRS2 autonomously affects β-cells, we have studied proliferation, apoptosis, and β-cell function in isolated rat and human islets after overexpression of IRS2 or IRS1. We found that β-cell proliferation was significantly increased in rat islets overexpressing IRS2 while IRS1 was less effective. Moreover, proliferation of a β-cell line, INS-1, was decreased after repression of Irs2 expression using RNA oligonucleotides. Overexpression of IRS2 in human islets significantly decreased apoptosis of β-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 β-cells from d-glucose-induced apoptosis. In addition, IRS2 can improve β-cell function. Our results indicate that IRS2 acts autonomously in β-cells in maintenance and expansion of functional β-cell mass in vivo.
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Authors
S. Mohanty, G.A. Spinas, K. Maedler, R.A. Zuellig, R. Lehmann, M.Y. Donath, T. Trüb, M. Niessen,