Activation of SOCS-3 by Resistin†
AUTOR(ES)
Steppan, Claire M.
FONTE
American Society for Microbiology
RESUMO
Resistin is an adipocyte hormone that modulates glucose homeostasis. Here we show that in 3T3-L1 adipocytes, resistin attenuates multiple effects of insulin, including insulin receptor (IR) phosphorylation, IR substrate 1 (IRS-1) phosphorylation, phosphatidylinositol-3-kinase (PI3K) activation, phosphatidylinositol triphosphate production, and activation of protein kinase B/Akt. Remarkably, resistin treatment markedly induces the gene expression of suppressor of cytokine signaling 3 (SOCS-3), a known inhibitor of insulin signaling. The 50% effective dose for resistin induction of SOCS-3 is ∼20 ng/ml, close to levels of resistin in serum. Association of SOCS-3 protein with the IR is also increased by resistin. Inhibition of SOCS function prevented resistin from antagonizing insulin action in adipocytes. SOCS-3 induction is the first cellular effect of resistin that is independent of insulin and is a likely mediator of resistin's inhibitory effect on insulin signaling in adipocytes.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=548000Documentos Relacionados
- Autoregulation of pituitary corticotroph SOCS-3 expression: Characterization of the murine SOCS-3 promoter
- Methylation of SOCS‐3 and SOCS‐1 in the carcinogenesis of Barrett's adenocarcinoma
- The central role of SOCS-3 in integrating the neuro-immunoendocrine interface
- SOCS-3 is frequently silenced by hypermethylation and suppresses cell growth in human lung cancer
- Inhibitory roles for SHP-1 and SOCS-3 following pituitary proopiomelanocortin induction by leukemia inhibitory factor