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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-6325

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

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Abstract

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.

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32 citations in Web of Science®
33 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Endocrinology and Diabetology
DDC:610 Medicine & health
Language:English
Date:2005
Deposited On:06 Apr 2009 07:16
Last Modified:28 Nov 2013 00:05
Publisher:Elsevier
ISSN:0014-4827
Publisher DOI:10.1016/j.yexcr.2004.09.011
PubMed ID:15572028

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