RGD Reference Report - The role of insulin receptor substrate-1 gene (IRS1) in type 2 diabetes in Pima Indians. - Rat Genome Database

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The role of insulin receptor substrate-1 gene (IRS1) in type 2 diabetes in Pima Indians.

Authors: Kovacs, P  Hanson, RL  Lee, YH  Yang, X  Kobes, S  Permana, PA  Bogardus, C  Baier, LJ 
Citation: Kovacs P, etal., Diabetes. 2003 Dec;52(12):3005-9.
RGD ID: 7207057
Pubmed: PMID:14633864   (View Abstract at PubMed)

The insulin receptor substrate-1 (IRS1) is a critical element in insulin-signaling pathways, and mutations in the IRS1 gene have been reported to have a role in determining susceptibility to traits related to type 2 diabetes. In gene expression studies of tissue biopsies from nondiabetic Pima Indians, IRS1 mRNA levels were reduced in adipocytes from obese subjects compared with lean subjects, and IRS1 mRNA levels were also reduced in skeletal muscle from insulin-resistant subjects compared with insulin-sensitive subjects (all P < 0.05). Based on these expression differences and the known physiologic role of IRS1, this gene was investigated as a candidate gene for susceptibility to type 2 diabetes in Pima Indians, a population with an extremely high incidence and prevalence of type 2 diabetes. Thirteen variants were identified, and among these variants, several were in complete linkage disequilibrium. Four genotypically unique variants were further genotyped in 937 DNA samples from full-heritage Pima Indians. Three of the variants were modestly associated with type 2 diabetes (P < 0.05), one of which was additionally associated with 2-h plasma insulin and glucose as well as insulin action at physiologic and maximally stimulating insulin concentrations (all P < 0.05). The association of variants in IRS1 with type 2 diabetes and type 2 diabetes-related phenotypes and the differential expression of IRS1 in adipocytes and skeletal muscle suggest a role of this gene in the pathogenesis of type 2 diabetes in Pima Indians.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
type 2 diabetes mellitus  IAGP 7207057DNA:SNP:promoter:-446G>A and -7120G>A (human)RGD 
type 2 diabetes mellitus  ISOIRS1 (Homo sapiens)7207057; 7207057DNA:SNP:promoter:-446G>A and -7120G>A (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Irs1  (insulin receptor substrate 1)

Genes (Mus musculus)
Irs1  (insulin receptor substrate 1)

Genes (Homo sapiens)
IRS1  (insulin receptor substrate 1)


Additional Information