Socs1 deficiency enhances hepatic insulin signaling
- Author(s)
- Jamieson, E; Chong, MMW; Steinberg, GR; Jovanovska, V; Fam, BC; Bullen, DVR; Chen, Y; Kemp, BE; Proietto, J; Kay, TWH; Andrikopoulos, S;
- Details
- Publication Year 2005-09-09,Volume 280,Issue #36,Page 31516-31521
- Journal Title
- JOURNAL OF BIOLOGICAL CHEMISTRY
- Publication Type
- Journal Article
- 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 interferon gamma 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.
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- Keywords
- ACTIVATED PROTEIN-KINASE; HUMAN SKELETAL-MUSCLE; METABOLISM IN-VIVO; CYTOKINE SIGNALING-1; RECEPTOR SUBSTRATE-2; INTERFERON-GAMMA; ISLET NEOGENESIS; MICE LACKING; BETA-CELLS; RESISTANCE
- Publisher's Version
- https://doi.org/10.1074/jbc.M502163200
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2005-09-09 12:00:00