Deletion of SOCS7 leads to enhanced insulin action and enlarged islets of Langerhans
Alexander S. Banks, … , Domenico Accili, Paul B. Rothman
Alexander S. Banks, … , Domenico Accili, Paul B. Rothman
Published September 1, 2005
Citation Information: J Clin Invest. 2005;115(9):2462-2471. https://doi.org/10.1172/JCI23853.
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Research Article Metabolism

Deletion of SOCS7 leads to enhanced insulin action and enlarged islets of Langerhans

Abstract

NIDDM is characterized by progressive insulin resistance and the failure of insulin-producing pancreatic β cells to compensate for this resistance. Hyperinsulinemia, inflammation, and prolonged activation of the insulin receptor (INSR) have been shown to induce insulin resistance by decreasing INSR substrate (IRS) protein levels. Here we describe a role for SOCS7 in regulating insulin signaling. Socs7-deficient mice exhibited lower glucose levels and prolonged hypoglycemia during an insulin tolerance test and increased glucose clearance in a glucose tolerance test. Six-month-old Socs7-deficient mice exhibited increased growth of pancreatic islets with mildly increased fasting insulin levels and hypoglycemia. These defects correlated with increased IRS protein levels and enhanced insulin action in cells lacking SOCS7. Additionally, SOCS7 associated with the INSR and IRS1 — molecules that are essential for normal regulation of insulin action. These data suggest that SOCS7 is a potent regulator of glucose homeostasis and insulin signaling.

Authors

Alexander S. Banks, Jianze Li, Lisa McKeag, Marta L. Hribal, Masaki Kashiwada, Domenico Accili, Paul B. Rothman

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Figure 5

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Resistance to stimulation-induced IRS1 degradation and increased adipoge...
Resistance to stimulation-induced IRS1 degradation and increased adipogenesis in Socs7-deficient cells. (A) Socs7+/+ (WT) or Socs7 –/ – (KO) MEF cells were serum starved for 14–16 hours before a 30-minute pretreatment without (lanes 1, 2, 5, and 6) or with (lanes 3, 4, 7, and 8) lactacystin (Lact), a proteasome inhibitor. Cells were then stimulated with 10 nM IGF-1 for 6 hours. Immunoblotting for IRS1 was performed, followed by membrane stripping and reprobing with anti-p85 as a protein loading control. (B) Wild-type and Socs7-, Socs1-, and Socs3-deficient MEF cells were subjected to adipocyte differentiation (see Methods). Differentiation was scored either by staining for oil red O to measure triglyceride accumulation or by (C) Q-PCR for Pparg (normalized to Hprt) relative to 3T3-L1 adipocytes during differentiation.