Socs1 deficiency enhances hepatic insulin signaling.

  • Jamieson E
  • Chong M
  • Steinberg G
 et al. 
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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 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.

Author-supplied keywords

  • Animals
  • Blood Glucose
  • Blood Glucose: biosynthesis
  • Carrier Proteins
  • Carrier Proteins: genetics
  • Carrier Proteins: physiology
  • Hypoglycemia
  • Hypoglycemia: genetics
  • Hypoglycemia: metabolism
  • Inflammation
  • Inflammation: prevention & control
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Insulin: physiology
  • Interferon-gamma
  • Interferon-gamma: deficiency
  • Interferon-gamma: genetics
  • Intracellular Signaling Peptides and Proteins
  • Liver
  • Liver: physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phosphoproteins
  • Phosphoproteins: metabolism
  • Repressor Proteins
  • Repressor Proteins: genetics
  • Repressor Proteins: physiology
  • Signal Transduction
  • Signal Transduction: physiology
  • Suppressor of Cytokine Signaling Proteins

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Authors

  • Emma Jamieson

  • Mark M W Chong

  • Gregory R Steinberg

  • Valentina Jovanovska

  • Barbara C Fam

  • Denise V R Bullen

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