Overexpression of Suppressor of Cytokine Signaling 3 in Adipose Tissue Causes Local but Not Systemic Insulin Resistance.
From: Division of Endocrinology, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215, USA.
Diabetes
- Publish Date: Mar 2006
- ISSN: 0012-1797
- Volume: 55
- Issue: 3
- Pages: 699-707
- Medium: Print
- Language: English
- Citation (JAMA): Shi Hang, Cave Belinda, Inouye Karen, et al. Overexpression of Suppressor of Cytokine Signaling 3 in Adipose Tissue Causes Local but Not Systemic Insulin Resistance.. Diabetes Mar 2006;55:699-707
Abstract
In adipocytes, suppressor of cytokine signaling (SOCS)3 deficiency increases insulin-stimulated insulin receptor substrate (IRS)-1 and -2 phosphorylation, IRS-associated phosphatidylinositol 3 kinase activity, and insulin-stimulated glucose uptake. Moreover, SOCS3 is required for tumor necrosis factor-alpha full inhibition of insulin-stimulated IRS-1 and -2 phosphorylation, phosphatidylinositol 3 kinase activity, and glucose uptake. Whether SOCS3 also inhibits adipocyte insulin signaling in vivo and whether this action further affects systemic insulin sensitivity is not clear. We therefore generated a transgenic mouse (aP2-SOCS3 mouse) overexpressing SOCS3 in adipose tissue. Overexpression of SOCS3 in adipocytes decreases IRS1 protein levels and subsequent insulin-stimulated IRS-1 and -2 phosphorylation, decreases p85 binding to IRS-1, and leads to decreased insulin-stimulated glucose uptake in adipocytes. This impaired insulin signaling in adipose tissue of aP2-SOCS3 mice causes decreased lipogenesis and blocks insulin’s antilipolytic action. However, because of decreased energy partitioning in adipose tissue, aP2-SOCS3 mice are resistant to diet-induced obesity and are protected against systemic insulin resistance caused by a high-fat diet. Therefore, overexpression of SOCS3 in adipocytes causes local adipocyte insulin resistance, but it is not sufficient to cause systemic insulin resistance.
Mesh Headings (Keywords): Adipocytes, Adipose Tissue, Animals, Blood Glucose, Energy Metabolism, Insulin, Insulin Resistance, Lipogenesis, Lipolysis, Mice, Mice, Inbred C57BL, Mice, Transgenic, Phenotype, Rabbits, Suppressor of Cytokine Signaling Proteins
Check for Full Text / PubMed Unique Identifier (PMID): 16505233
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