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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
1999-9-23
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pubmed:abstractText |
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+/- 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-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 beta-cell development and compensation for peripheral insulin resistance. To establish a role for the Igf-1 receptor in beta-cells, we intercrossed mice heterozygous for null alleles of Igf1r and Irs2. Our results reveal that Igf-1 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-1 in pancreatic beta-cells to maintain glucose homeostasis.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1061-4036
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
32-40
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:10471495-Age Factors,
pubmed-meshheading:10471495-Animals,
pubmed-meshheading:10471495-Apoptosis,
pubmed-meshheading:10471495-Blood Glucose,
pubmed-meshheading:10471495-Body Weight,
pubmed-meshheading:10471495-Female,
pubmed-meshheading:10471495-Gene Expression Regulation, Developmental,
pubmed-meshheading:10471495-Glucose Tolerance Test,
pubmed-meshheading:10471495-Insulin,
pubmed-meshheading:10471495-Insulin Receptor Substrate Proteins,
pubmed-meshheading:10471495-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:10471495-Islets of Langerhans,
pubmed-meshheading:10471495-Liver,
pubmed-meshheading:10471495-Male,
pubmed-meshheading:10471495-Mice,
pubmed-meshheading:10471495-Mice, Knockout,
pubmed-meshheading:10471495-Muscle, Skeletal,
pubmed-meshheading:10471495-Pancreas,
pubmed-meshheading:10471495-Phosphoproteins,
pubmed-meshheading:10471495-Receptor, IGF Type 1,
pubmed-meshheading:10471495-Signal Transduction,
pubmed-meshheading:10471495-Time Factors
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pubmed:year |
1999
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pubmed:articleTitle |
Irs-2 coordinates Igf-1 receptor-mediated beta-cell development and peripheral insulin signalling.
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pubmed:affiliation |
Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, Massachusetts 02215, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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