par Marion, Evelyne 
;Kaisaki, P. J.;Pouillon, Valérie ;Gueydan, Cyril ;Levy, Jacques ;Bodson, André;Krzentowski, Georges;Daubresse, J. C.;Mockel, Jean ;Behrends, Jens ;Servais, Gaëtan ;Szpirer, Claude ;Kruys, Véronique ;Gauguier, D.;Schurmans, Stéphane
Référence Diabetes, 51, page (2012-2016)
Publication Publié, 2002
;Kaisaki, P. J.;Pouillon, Valérie ;Gueydan, Cyril ;Levy, Jacques ;Bodson, André;Krzentowski, Georges;Daubresse, J. C.;Mockel, Jean ;Behrends, Jens ;Servais, Gaëtan ;Szpirer, Claude ;Kruys, Véronique ;Gauguier, D.;Schurmans, Stéphane Référence Diabetes, 51, page (2012-2016)
Publication Publié, 2002
Article révisé par les pairs
| Résumé : | 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. |
