Source:http://linkedlifedata.com/resource/pubmed/id/16644711
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
|
| pubmed:dateCreated |
2006-4-28
|
| pubmed:abstractText |
Diminished insulin sensitivity is a characteristic feature of type 2 diabetes. Inhibition of insulin action, resulting in reduced skeletal muscle glucose uptake, is mediated in part through stimulation of RhoA activity. One regulator of RhoA activity is leukemia-associated Rho guanine nucleotide exchange factor (LARG). The LARG gene maps to a region on chromosome 11q23-24 that shows genetic linkage to BMI and type 2 diabetes in Pima Indians. Because of its role in RhoA activation, the LARG gene was analyzed as a positional candidate gene for this linkage. Sequencing of the LARG gene and genotyping of variants identified several polymorphisms that were associated with in vivo rates of insulin-mediated glucose uptake, at both physiological and maximally stimulating insulin concentrations, among 322 nondiabetic Pima Indians who had undergone a hyperinsulinemic-euglycemic clamp. The strongest association with rate of glucose uptake was found with a Tyr1306Cys polymorphism (P < 0.0001, adjusted for age, sex, percent body fat, and nuclear family membership). In transient transfection studies in NIH3T3 cells, the LARG(Cys1306) protein had reduced activity compared with LARG(Tyr1306) protein (P < 0.05). We propose that the Tyr1306Cys substitution in LARG, through its differential activation of RhoA, increases insulin sensitivity in nondiabetic Pima Indians.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
May
|
| pubmed:issn |
0012-1797
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
55
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1497-503
|
| pubmed:dateRevised |
2011-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:16644711-3T3 Cells,
pubmed-meshheading:16644711-Amino Acid Substitution,
pubmed-meshheading:16644711-Animals,
pubmed-meshheading:16644711-Arizona,
pubmed-meshheading:16644711-Chromosome Mapping,
pubmed-meshheading:16644711-Chromosomes, Human, Pair 11,
pubmed-meshheading:16644711-Diabetes Mellitus, Type 2,
pubmed-meshheading:16644711-Ethnic Groups,
pubmed-meshheading:16644711-Genetic Variation,
pubmed-meshheading:16644711-Guanine Nucleotide Exchange Factors,
pubmed-meshheading:16644711-Humans,
pubmed-meshheading:16644711-Indians, North American,
pubmed-meshheading:16644711-Insulin,
pubmed-meshheading:16644711-Longitudinal Studies,
pubmed-meshheading:16644711-Mice,
pubmed-meshheading:16644711-Muscle, Skeletal,
pubmed-meshheading:16644711-Polymorphism, Single Nucleotide,
pubmed-meshheading:16644711-Reference Values,
pubmed-meshheading:16644711-Transfection
|
| pubmed:year |
2006
|
| pubmed:articleTitle |
A functional Tyr1306Cys variant in LARG is associated with increased insulin action in vivo.
|
| pubmed:affiliation |
Diabetes Molecular Genetics Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 445 North 5th Street, Phoenix, AZ 85004, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Intramural
|