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PMID: 10606633 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Altered function of insulin receptor substrate-1-deficient mouse islets and cultured beta-cell lines.

The Journal of clinical investigation ·Vol. 104 ·No. 12 ·1999-12-00 ·Pages R69-75

Kulkarni RN, Winnay JN, Daniels M, Brüning JC, Flier SN, Hanahan D, Kahn CR

Abstract

Insulin receptor substrate-1 (IRS-1) is pivotal in mediating the actions of insulin and growth factors in most tissues of the body, but its role in insulin-producing beta islet cells is unclear. Freshly isolated islets from IRS-1 knockout mice and SV40-transformed IRS-1-deficient beta-cell lines exhibit marked insulin secretory defects in response to glucose and arginine. Furthermore, insulin expression is reduced by about 2-fold in the IRS-1-null islets and beta-cell lines, and this defect can be partially restored by transfecting the cells with IRS-1. These data provide evidence for an important role of IRS-1 in islet function and provide a novel functional link between the insulin signaling and insulin secretion pathways. This article may have been published online in advance of the print edition. The date of publication is available from the JCI website, http://www.jci.org.

MeSH Terms
Animals Cell Line Glucagon/metabolism Insulin/analysis,metabolism Insulin Receptor Substrate Proteins Insulin Secretion Islets of Langerhans/chemistry,physiology Mice Mice, Inbred C57BL Mice, Knockout Phosphoproteins/analysis,deficiency,physiology Reverse Transcriptase Polymerase Chain Reaction
Chemicals
Insulin Insulin Receptor Substrate Proteins Irs1 protein, mouse Phosphoproteins Glucagon
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Kulkarni R N
Division of Cellular and Molecular Physiology, Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA.
Winnay J N
Daniels M
Brüning J C
Flier S N
Hanahan D
Kahn C R
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI8339
Published
1999-12-00
Pages
R69-75
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC409887
Subset
IM
Grants
NIDDK NIH HHS · P30 DK-36836 · United States
NIDDK NIH HHS · F32 DK009825 · United States
NIDDK NIH HHS · DK-09825-02 · United States
NIDDK NIH HHS · P30 DK036836 · United States
NIDDK NIH HHS · DK-31036 · United States
NIDDK NIH HHS · R37 DK031036 · United States
NIDDK NIH HHS · R01 DK031036 · United States
External Links
PubMed source DOI: 10.1172/JCI8339 PMC Full Text View journal details
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