Insulin sensitivity gets a kick out of SOCS-7

Insulin resistance is a fundamental factor in non-insulin-dependent diabetes. Prolonged activation of the insulin receptor, inflammation, and excessive insulin levels can induce insulin resistance by decreasing levels of insulin receptor substrate (IRS) proteins. However, the mechanism(s) underlying the destruction of IRS proteins and subsequent resistance to insulin have not been well defined. Proteins of the SOCS family have been implicated in the negative regulation of insulin signaling and also regulate cytokine signaling by targeting proteins for degradation by the proteasome. In particular, the function for the SOCS-7 protein was previously unclear.

In a study appearing online on August 25 in advance of print publication of the September 1 issue of the Journal of Clinical Investigation, Paul Rothman and colleagues from the University of Iowa demonstrate that SOCS-7 regulates insulin signaling by associating with several components of the insulin-signaling cascade.

The researchers generate SOCS-7-deficient mice and show that cells lacking SOCS-7 have increased IRS protein levels and prolonged IRS activation. SOCS-7 deficient mice are more insulin sensitive as measured by a glucose tolerance test and an insulin tolerance test. In addition, SOCS-7-deficient mice exhibit increased growth of pancreatic islets with increased fasting insulin levels and hypoglycemia. As one of the only mouse knockout models featuring increased insulin sensitivity, these data suggest that SOCS-7 is a potent regulator of glucose homeostasis and insulin signaling.

TITLE: Deletion of SOCS7 leads to enhanced insulin action and enlarged islets of langerhans

AUTHOR CONTACT:
Paul B. Rothman
University of Iowa, Iowa City, IA USA
Phone: 319 384 5424; Fax: 319 356 8608; E-mail: paul-rothman@uiowa.edu

View the PDF of this article at: https://www.the-jci.org/article.php?id=23853