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Socs1 deficiency enhances hepatic insulin signaling

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

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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: https://doi.org/10.1074/jbc.M502163200
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Citations in Scopus: 32 - View on Scopus

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