In:
Diabetes, American Diabetes Association, Vol. 51, No. 7 ( 2002-07-01), p. 2012-2017
Abstract:
Genetic susceptibility to type 2 diabetes involves many genes, most of which are still unknown. The lipid phosphatase SHIP2 is a potent negative regulator of insulin signaling and sensitivity in vivo and is thus a good candidate gene. Here we report the presence of SHIP2 gene mutations associated with type 2 diabetes in rats and humans. The R1142C mutation specifically identified in Goto-Kakizaki (GK) and spontaneously hypertensive rat strains disrupts a potential class II ligand for Src homology (SH)-3 domain and slightly impairs insulin signaling in cell culture. In humans, a deletion identified in the SHIP2 3′ untranslated region (UTR) of type 2 diabetic subjects includes a motif implicated in the control of protein synthesis. In cell culture, the deletion results in reporter messenger RNA and protein overexpression. Finally, genotyping of a cohort of type 2 diabetic and control subjects showed a significant association between the deletion and type 2 diabetes. Altogether, our results show that mutations in the SHIP2 gene contribute to the genetic susceptibility to type 2 diabetes in rats and humans.
Type of Medium:
Online Resource
ISSN:
0012-1797
,
1939-327X
DOI:
10.2337/diabetes.51.7.2012
Language:
English
Publisher:
American Diabetes Association
Publication Date:
2002
detail.hit.zdb_id:
1501252-9
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