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 3

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Increased insulin sensitivity in Socs7 –/ – mice. (A) Blood glucose (rig...
Increased insulin sensitivity in Socs7 –/ – mice. (A) Blood glucose (right) and plasma insulin (left) concentrations in overnight-fasted wild-type and Socs7 –/ – mice aged at least 6 months. (B) Prolonged hypoglycemia in Socs7 –/ – mice following ITT and increased glucose clearance in GTT. All values are expressed as the mean ± SEM obtained from wild-type and Socs7 –/ – mice. All tests were performed on 5- to 8-month-old mice. Filled circles, wild-type mice; open circles, Socs7 –/ – mice. *P < 0.05; **P < 0.01; ***P < 0.001 (1-tailed Student’s t test). For ITT, results are given as a percentage of basal glucose concentration. (C) Increased islet size and β cell mass in Socs7 –/ – mice compared with wild-type littermates as assayed by staining with anti-insulin (upper panels) and antiglucagon antibodies (lower panels). Histogram represents the quantization of islet size performed using SPOT imaging software. Black bars, wild-type mice; white bars, Socs7 –/ – mice. Magnification, ×10.