Socs1 deficiency enhances hepatic insulin signaling

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Jamieson, Emma, Chong, Mark M. W, Steinberg, Gregory R, Jovanovska, Valentina, Fam, Barbara C, Bullen, Denise V. R, Chen, Ye, Kemp, Bruce E, Proietto, Joseph, Kay, Thomas W. H and Andrikopoulos, Sofianos (2005) Socs1 deficiency enhances hepatic insulin signaling. Journal of Biological Chemistry, 280 (36). pp. 31516-31521. ISSN 0021-9258

Abstract

Suppressor of cytokine signaling 1 (SOCS1) is an intracellular inhibitor of cytokine, growth factor, and hormone signaling. Socs1–/– mice die before weaning from a multiorgan inflammatory disease. Neonatal Socs1–/– mice display severe hypoglycemia and hypoinsulinemia. Concurrent interferonγ gene deletion (Ifng–/–) prevented inflammation and corrected the hypoglycemia. In hyperinsulinemic clamp studies, however, Socs1–/–Ifng–/– mice had enhanced hepatic insulin sensitivity demonstrated by greater suppression of endogenous glucose production compared with controls with no difference in glucose disposal. Socs1–/–Ifng–/– mice had elevated liver insulin receptor substrate 2 expression (IRS-2) and IRS-2 tyrosine phosphorylation. This was associated with lower phosphoenolpyruvate carboxykinase mRNA expression. These effects were not associated with elevated hepatic AMP-activated protein kinase activity. Hepatic insulin sensitivity and IRS-2 levels play central roles in the pathogenesis of type 2 diabetes. Socs1 deficiency increases IRS-2 expression and enhances hepatic insulin sensitivity in vivo indicating that inhibition of SOCS1 may be a logical strategy in type 2 diabetes.

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Additional Information

Online ISSN: 1083-351X

Item type Article
URI https://vuir.vu.edu.au/id/eprint/8109
DOI https://doi.org/10.1074/jbc.M502163200
Official URL http://dx.doi.org/10.1074/jbc.M502163200
Subjects Historical > Faculty/School/Research Centre/Department > School of Biomedical and Health Sciences
Current > FOR Classification > 1101 Medical Biochemistry and Metabolomics
Keywords ResPubID22159. hepatic insulin signalling, liver, SOCS1, cytokine, mice, hypoglycemia, glucose, type 2 diabetes
Citations in Scopus 32 - View on Scopus
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