SOCS3 inhibits insulin signaling in porcine primary adipocytes
- 304 Downloads
Insulin resistance is a major player in the pathogenesis of type II diabetes, the metabolic syndrome, and obesity. SOCS3 plays an important role in the development of insulin resistance. To investigate the role of SOCS3 in porcine adipocyte insulin signaling, we first detected the effect of insulin on SOCS3 mRNA and protein expression in porcine primary adipocytes by real-time RT-PCR and Western blotting. Then, we constructed a recombinant adenovirus encoding SOCS3 gene (Ad-SOCS3) which was used to infect differentiated porcine primary adipocytes for 3 days. The expression and phosphorylation of main insulin signaling components were detected by Western blotting. The results showed that 100 nM insulin could induce SOCS3 mRNA expression but not protein expression, and overexpression of SOCS3 decreased IRS1 protein level, insulin-stimulated IRS1 tyrosine phosphorylation, PI3K activation, and Akt phosphorylation, but increased IRS1 serine phosphorylation in porcine primary adipocytes. These results indicate that SOCS3 is an important negative regulator of insulin signaling in porcine adipocytes. Thus, SOCS3 may be a novel therapeutic target for the prevention or treatment of insulin resistance and type II diabetes.
KeywordsSOCS3 Insulin signaling Porcine primary adipocytes Phosphorylation
This study was supported by The National High Technology Research and Development Program (No. 2006AA10Z138) and Key and Specific National Project for Creating New Biological Species Transgenically (No. 2008ZX08006-005) of China. We thank Dr. Bin Wu and Dr. J. Gale for their suggestions and correction of the English manuscript.
- 1.Lillioja S, Mott DM, Spraul M, Ferraro R, Foley JE, Ravussin E, Knowler WC, Bennett PH, Bogardus C (1993) Insulin-resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes-mellitus—prospective studies of pima-indians. N Engl J Med 329:1988–1992CrossRefPubMedGoogle Scholar
- 4.Buchanan TA, Xiang AH, Peters RK, Kjos SL, Marroquin A, Goico J, Ochoa C, Tan S, Berkowitz K, Hodis HN, Azen SP (2002) Preservation of pancreatic beta-cell function and prevention of type II diabetes by pharmacological treatment of insulin resistance in high-risk hispanic women. Diabetes 51:2796–2803CrossRefPubMedGoogle Scholar
- 10.Endo TA, Masuhara M, Yokouchi M, Suzuki R, Sakamoto H, Mitsui K, Matsumoto A, Tanimura S, Ohtsubo M, Misawa H, Miyazaki T, Leonor N, Taniguchi T, Fujita T, Kanakura Y, Komiya S, Yoshimura A (1997) A new protein containing an SH2 domain that inhibits JAK kinases. Nature 387:921–924CrossRefPubMedGoogle Scholar
- 14.Zhang JG, Farley A, Nicholson SE, Willson TA, Zugaro LM, Simpson RJ, Moritz RL, Cary D, Richardson R, Hausmann G, Kile BJ, Kent SB, Alexander WS, Metcalf D, Hilton DJ, Nicola NA, Baca M (1999) The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation. Proc Natl Acad Sci USA 96:2071–2076CrossRefPubMedGoogle Scholar
- 17.Krebs DL, Hilton DJ (2003) A new role for SOCS in insulin action. Suppressor of cytokine signaling. Sci STKE 2003: PE6Google Scholar