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Socs1 deficiency enhances hepatic insulin signaling

Jamieson, Emma and Chong, Mark M. W and Steinberg, Gregory R and Jovanovska, Valentina and Fam, Barbara C and Bullen, Denise V. R and Chen, Ye and Kemp, Bruce E and Proietto, Joseph and 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

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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.

Item Type: Article
Additional Information:

Online ISSN: 1083-351X

Uncontrolled Keywords: ResPubID22159. hepatic insulin signalling, liver, SOCS1, cytokine, mice, hypoglycemia, glucose, type 2 diabetes
Subjects: Faculty/School/Research Centre/Department > School of Biomedical and Health Sciences
FOR Classification > 1101 Medical Biochemistry and Metabolomics
Depositing User: VUIR
Date Deposited: 22 Dec 2011 23:23
Last Modified: 10 Mar 2015 03:45
URI: http://vuir.vu.edu.au/id/eprint/8109
DOI: 10.1074/jbc.M502163200
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Citations in Scopus: 25 - View on Scopus

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