Irs-2 coordinates Igf-1 receptor-mediated β-cell development and peripheral insulin signalling

被引：443

作者：

Withers, DJ ^{[1
]}

Burks, DJ ^{[1
]}

Towery, HH ^{[1
]}

Altamuro, SL ^{[1
]}

Flint, CL ^{[1
]}

White, ME ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Howard Hughes Med Inst, Joslin Diabet Ctr, Boston, MA 02215 USA

来源：

NATURE GENETICS | 1999年 / 23卷 / 01期

关键词：

D O I：

10.1038/12631

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Insulin receptor substrates (Irs proteins) mediate the pleiotropic effects of insulin and Igf-l (insulin-like growth factor-1), including regulation of glucose homeostasis and cell growth and survival. We intercrossed mice heterozygous for two null alleles (Irs1(+/-) and Irs2(+/-)) 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-l having the predominant role. By contrast, both Irs-l and Irs-2 function in peripheral carbohydrate metabolism, but Irs-2 has the major role in beta-cell development and compensation for peripheral insulin resistance. To establish a role for the Igf-l receptor in beta-cells, we intercrossed mice heterozygous for null alleles of Igf1r and Irs2. Our results reveal that Igf-l receptors promote beta-cell development and survival through the Irs-2 signalling pathway. Thus, Irs-2 integrates the effects of insulin in peripheral target tissues with Igf-l in pancreatic beta-cells to maintain glucose homeostasis.

引用

页码：32 / 40

页数：9

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