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- Title
Irs-2 coordinates Igf-1 receptor-mediated β-cell development and peripheral insulin signalling.
- Authors
Withers, Dominic J.; Burks, Deborah J.; Towery, Heather H.; Altamuro, Shari L.; Flint, Carrie L.; White, Morris F.
- Abstract
Insulin receptor substrates (Irs proteins) mediate the pleiotropic effects of insulin and Igf-1 (insulin-like growth factor-1), including regulation of glucose homeostasis and cell growth and survival. We intercrossed mice heterozygous for two null alleles (Irs1[sup +/-] and Irs2[sup +/-]) and investigated growth and glucose metabolism in mice with viable genotypes. Our experiments revealed that Irs-1 and Irs-2 are critical for embryonic and post-natal growth, with Irs-1 having the predominant role. By contrast, both Irs-1 and Irs-2 function in peripheral carbohydrate metabolism, but Irs-2 has the major role in β-cell development and compensation for peripheral insulin resistance. To establish a role for the Igf-1 receptor in β-cells, we intercrossed mice heterozygous for null alleles of Igf1r and Irs2. Our results reveal that Igf-1 receptors promote β-cell development and survival through the Irs-2 signalling pathway. Thus, Irs-2 integrates the effects of insulin in peripheral target tissues with Igf-1 in pancreatic β-cells to maintain glucose homeostasis.
- Subjects
INSULIN receptors; SOMATOMEDIN; MICE
- Publication
Nature Genetics, 1999, Vol 23, Issue 1, p32
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/12631