Source:http://linkedlifedata.com/resource/pubmed/id/12176670
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
|
| pubmed:dateCreated |
2002-8-14
|
| pubmed:abstractText |
Insulin receptor substrate 1 (IRS-1) gene polymorphisms have been identified in type 2 diabetic patients; however, it is unclear how such polymorphisms contribute to the development of diabetes. Here we introduced obesity in heterozygous IRS-1 knockout (IRS-1(+/-)) mice by gold-thioglucose (GTG) injection and studied the impact of reduced IRS-1 expression on obesity-linked insulin resistance. GTG injection resulted in approximately 30% weight gain in IRS-1(+/-) and wild type (WT) mice, compared with saline-injected controls. There was no difference in insulin sensitivity between lean IRS-1(+/-) and lean WT. Elevated fasting insulin levels but no change in fasting glucose were noted in obese IRS-1(+/-) and WT compared with the respective lean controls. Importantly, fasting insulin in obese IRS-1(+/-) was 1.5-fold higher (P<0.05) than in obese WT, and an insulin tolerance test showed a profound insulin resistance in obese IRS-1(+/-) compared with obese WT. The islets of obese IRS-1(+/-) were 1.4-fold larger than those of obese WT. The expression of insulin receptor and IRS-1 and IRS-2 was decreased in obese IRS-1(+/-), which could in part explain the profound insulin resistance in these mice. Our results suggest that IRS-1 is the suspected gene for type 2 diabetes and its polymorphisms could worsen insulin resistance in the presence of other additional factors, such as obesity.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Aurothioglucose,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin Receptor Substrate Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Irs1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Irs2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Insulin
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
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| pubmed:issn |
0022-0795
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
174
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
309-19
|
| pubmed:dateRevised |
2011-11-17
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| pubmed:meshHeading |
pubmed-meshheading:12176670-Animals,
pubmed-meshheading:12176670-Aurothioglucose,
pubmed-meshheading:12176670-Diabetes Mellitus, Type 2,
pubmed-meshheading:12176670-Insulin,
pubmed-meshheading:12176670-Insulin Receptor Substrate Proteins,
pubmed-meshheading:12176670-Insulin Resistance,
pubmed-meshheading:12176670-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:12176670-Liver,
pubmed-meshheading:12176670-Male,
pubmed-meshheading:12176670-Mice,
pubmed-meshheading:12176670-Mice, Knockout,
pubmed-meshheading:12176670-Models, Animal,
pubmed-meshheading:12176670-Muscle, Skeletal,
pubmed-meshheading:12176670-Obesity,
pubmed-meshheading:12176670-Pancreas,
pubmed-meshheading:12176670-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:12176670-Phosphoproteins,
pubmed-meshheading:12176670-Receptor, Insulin
|
| pubmed:year |
2002
|
| pubmed:articleTitle |
Heterozygous knockout of the IRS-1 gene in mice enhances obesity-linked insulin resistance: a possible model for the development of type 2 diabetes.
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| pubmed:affiliation |
Department of Metabolic Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|