| First Author | Shi H | Year | 2006 |
| Journal | Diabetes | Volume | 55 |
| Issue | 3 | Pages | 699-707 |
| PubMed ID | 16505233 | Mgi Jnum | J:106855 |
| Mgi Id | MGI:3619682 | Doi | 10.2337/diabetes.55.03.06.db05-0841 |
| Citation | Shi H, et al. (2006) Overexpression of suppressor of cytokine signaling 3 in adipose tissue causes local but not systemic insulin resistance. Diabetes 55(3):699-707 |
| abstractText | 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. |
