当前位置： SCI文献检索 > LIFE SCIENCES期刊下所有文献 > Insulin receptor and IRS-1 co-immunoprecipitation with SOCS-3, and IKKα/β phosphorylation are increased in obese Zucker rat skeletal muscle.

Insulin receptor and IRS-1 co-immunoprecipitation with SOCS-3, and IKKα/β phosphorylation are increased in obese Zucker rat skeletal muscle.

Abstract：

AIMS:We evaluated if selected pro-inflammatory cytokines and/or the protein suppressor of cytokine signaling 3 (SOCS-3) could account for decreased insulin-stimulated phosphatidylinositol 3-kinase (PI3-K) activity in the skeletal muscle of the obese Zucker rat. MAIN METHODS:Eight lean and eight obese Zucker rats ~4weeks of age were obtained and allowed to feed ad libitum for 4weeks before undergoing hind limb perfusion in the presence of 500μU/ml insulin. KEY FINDINGS:Insulin-stimulated skeletal muscle PI3-K activity and 3-O-methylglucose transport rates were reduced (P<0.05) in obese compared to lean animals. IRS-1 concentration remained unchanged although IRS-1 tyrosine phosphorylation was decreased (P<0.05), and IRS-1 serine phosphorylation (pS) was increased (P<0.05) in obese animals compared to lean animals. IKKα/β pS and JNK theronine/tyrosine phosphorylation was increased (P<0.05) in the obese animals. IκBα concentration was decreased (P<0.05) and IκBα pS was increased (P<0.05) in the obese compared to lean Zucker animals. SOCS-3 concentration and SOCS-3 co-immunoprecipitation with both insulin receptor β-subunit (IR-β) and IRS-1 were elevated (P<0.05) in obese compared to lean animals. IRS-1 co-immunoprecipitation with IR-β was reduced 56% in the obese animals. SIGNIFICANCE:Increased IKKα/β and JNK serine phosphorylation may contribute to increasing IRS-1 serine phosphorylation, while concurrent co-localization of SOCS-3 with both IR-β and IRS-1 may prevent IRS-1 from interacting with IR-β. These two mechanisms thusly may independently contribute to impairing insulin-stimulated PI3-K activation in the skeletal muscle of the obese Zucker rat.

journal_name

Life Sci

journal_title

Life sciences

authors

Zolotnik IA,Figueroa TY,Yaspelkis BB 3rd

doi

10.1016/j.lfs.2012.08.038

subject

Has Abstract

pub_date

2012-10-22 00:00:00

pages

816-22

issue

15-16

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(12)00490-0

journal_volume

91

pub_type

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