Socs1 deficiency enhances hepatic insulin signaling

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 interferony 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)..