| IRS-3 inhibits IRS-2-mediated signaling in pancreatic beta-cells. | |
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MedLine Citation:
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PMID: 12850284 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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IRS-2 plays an important role in the control of pancreatic beta-cell growth, however it is unclear if other IRS family members are also involved. Using recombinant adenoviruses, IRS-1, -2 and -3 expression was varied in the beta-cell line, INS-1. Increased IRS-1 expression had no appreciable effect on beta-cell growth. However, increased IRS-2 expression augmented glucose/IGF-1 induced beta-cell growth mitogenesis and decreased apoptosis due to glucose-deprivation. In contrast, increased IRS-3 expression significantly inhibited mitogenesis and increased apoptosis. IRS-3 was intransiently located to the beta-cell plasma membrane, and appeared to be inert in terms of IGF-1 induced signaling. However, increased IRS-3 expression blocked glucose/IGF-1 induced IRS-2 translocation from the cytosol to the plasma membrane, dampening IRS-2/IGF-1R interaction and subsequent activation of the PI3K/PKB/GSK3 signaling pathway. In contrast, glucose/IGF-1 induced Erk-1/-2 and p70S6K activation were unaffected by IRS-3. These data emphasize the importance of IRS-2/PI3K/PKB signal transduction for beta-cell growth and survival. |
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Authors:
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Melissa K Lingohr; Lorna M Dickson; Christian E Wrede; Jill F McCuaig; Martin G Myers; Christopher J Rhodes |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Molecular and cellular endocrinology Volume: 204 ISSN: 0303-7207 ISO Abbreviation: Mol. Cell. Endocrinol. Publication Date: 2003 Jun |
Date Detail:
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Created Date: 2003-07-09 Completed Date: 2004-04-30 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 7500844 Medline TA: Mol Cell Endocrinol Country: Ireland |
Other Details:
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Languages: eng Pagination: 85-99 Citation Subset: IM |
Affiliation:
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Pacific Northwest Research Institute, Seattle, WA 98122, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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1-Phosphatidylinositol 3-Kinase
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metabolism Animals Apoptosis Cell Division Glucose / pharmacology Insulin Receptor Substrate Proteins Insulin-Like Growth Factor I / pharmacology Intracellular Signaling Peptides and Proteins Islets of Langerhans / cytology, metabolism* Male Phosphoproteins / genetics, metabolism, physiology* Rats Rats, Sprague-Dawley Signal Transduction* Transfection |
| Grant Support | |
ID/Acronym/Agency:
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DK55269/DK/NIDDK NIH HHS; DK60266/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Insulin Receptor Substrate Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/Irs1 protein, rat; 0/Irs2 protein, rat; 0/Irs3 protein, rat; 0/Phosphoproteins; 50-99-7/Glucose; 67763-96-6/Insulin-Like Growth Factor I; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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