Fibroblast growth factor-21 protects human skeletal muscle myotubes from palmitate-induced insulin resistance by inhibiting stress kinase and NF-κB

被引：77

作者：

Lee, Min Suk ^{[1
]}

Choi, Sung-E ^{[1
]}

Ha, Eun Suk ^{[1
]}

An, So-Yeon ^{[1
]}

Kim, Tae Ho ^{[2
]}

Han, Seung Jin ^{[1
]}

Kim, Hae Jin ^{[1
]}

Kim, Dae Jung ^{[1
]}

Kang, Yup ^{[3
]}

Lee, Kwan-Woo ^{[1
]}

机构：

[1] Ajou Univ, Sch Med, Dept Endocrinol & Metab, Suwon 443721, South Korea

[2] Kwandong Univ, Coll Med, Myongji Hosp, Div Endocrinol,Dept Internal Med, Goyang, South Korea

[3] Ajou Univ, Sch Med, Inst Med Sci, Suwon 443721, South Korea

来源：

METABOLISM-CLINICAL AND EXPERIMENTAL | 2012年 / 61卷 / 08期

关键词：

TUMOR-NECROSIS-FACTOR; PPAR-ALPHA; TARGETED DISRUPTION; METABOLIC REGULATOR; DIABETES-MELLITUS; IN-VIVO; GLUCOSE; SENSITIVITY; OBESITY; ACTIVATION;

D O I：

10.1016/j.metabol.2012.01.012

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

We investigated the effects of fibroblast growth factor-21 (FGF-21) on palmitate-induced insulin resistance in skeletal muscle myotubes. First, to determine the effect of FGF-21 on palmitate-induced insulin resistance, we measured 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-o-glucose uptake and levels of proteins involved in insulin signaling pathways (IRS-1 and Akt) in human skeletal muscle myotubes (HSMMs) exposed to palmitate for 24 h, and compared HSMMs exposed to palmitate and different doses of recombinant FGF-21. Second, to determine the mechanisms underlying the contribution of FGF-21 to palmitate-induced insulin resistance, we compared levels of proteins linked to palmitate-induced insulin resistance (PKC-theta, IKK alpha/beta, JNK, p38, I kappa B alpha, and NF-kappa B) in HSMMs exposed to palmitate and different doses of recombinant FGF-21 for 24 h. Palmitate-reduced glucose uptake was restored by FGF-21. Palmitate inhibited phosphorylation of Akt and thereby impaired insulin signaling in HSMMs. FGF-21 prevented palmitate from inhibiting the phosphorylation of Akt. These results indicate that FGF-21 prevented palmitate-induced insulin resistance in HSMMs. Palmitate activated NF-kappa B in HSMMs, thereby impairing the action of insulin and initiating chronic inflammation. FGF-21 inhibited palmitate-induced NF-kappa B activation in HSMMs. The results of the present study suggest that FGF-21 prevents palmitate-induced insulin resistance in HSMMs by inhibiting the activation of stress kinase and NF-kappa B. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：1142 / 1151

页数：10