Overexpression of IRS2 in isolated pancreatic islets causes proliferation and protects human {beta}-cells from hyperglycemia-induced apoptosis

Journal Article · Tue Feb 01 00:00:00 EST 2005 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2004.09.011· OSTI ID:20717523

Mohanty, S ^[1]; Spinas, G A ^[1]; Maedler, K ^[1]; Zuellig, R A ^[1]; Lehmann, R ^[1]; Donath, M Y ^[1]; Trueb, T ^[2]; Niessen, M ^[1]

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1. Division of Endocrinology and Diabetes, University Hospital of Zurich, 8091 Zurich (Switzerland)
2. Universitaetsverwaltung, Stab fuer Sachmittel-Kredite, KUN110, Kuenstlergasse 15, 8001 Zurich (Switzerland)

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.

• OSTI ID: 20717523
• Journal Information: Experimental Cell Research, Vol. 303, Issue 1; Other Information: DOI: 10.1016/j.yexcr.2004.09.011; PII: S0014-4827(04)00536-1; Copyright (c) 2004 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMP
APOPTOSIS
CELL PROLIFERATION
ENZYMES
FLUORESCENCE
GLUCOSE
HEXADECANOIC ACID
IN VIVO
INSULIN
LEAD SULFIDES
OLIGONUCLEOTIDES
PANCREAS
PHOSPHATES
RATS
RECEPTORS
RNA