Melanocortin-4 receptor activation inhibits c-Jun N-terminal kinase activity and promotes insulin signaling

被引：43

作者：

Chai, Biaoxin ^{[1
]}

Li, Ji-Yao ^{[1
]}

Zhang, Weizhen ^{[1
]}

Wang, Hui ^{[1
]}

Mulholland, Michael W. ^{[1
]}

机构：

[1] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA

来源：

PEPTIDES | 2009年 / 30卷 / 06期

关键词：

c-Jun N-terminal kinase (JNK); Melanocortin receptor; AKT; Insulin; Insulin receptor substrate 1 (IRS-1); MT II; NDP-MSH; Hypothalamus; MELANOCYTE-STIMULATING HORMONE; MAP KINASE; PHOSPHORYLATION; PROTEIN; OBESITY; PATHWAYS; JNK; SUBSTRATE-1; EXPRESSION; PEPTIDES;

D O I：

10.1016/j.peptides.2009.03.006

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The melanocortin system is crucial to regulation of energy homeostasis. The melanocortin receptor type 4 (MC4R) modulates insulin signaling via effects on c-Jun N-terminal kinase (INK). The melanocortin agonist NDP-MSH dose-dependently inhibited INK activity in HEK293 cells stably expressing the human MC4R; effects were reversed by melanocortin receptor antagonist. NDP-MSH time- and dose-dependently inhibited IRS-1(ser307) phosphorylation, effects also reversed by a specific melanocortin receptor antagonist. NDP-MSH augmented insulin-stimulated AKT phosphorylation in vitro. The melanocortin agonist melanotan II increased insulin-stimulated AKT phosphorylation in the rat hypothalamus in vivo. NDP-MSH increased insulin-stimulated glucose uptake in hypothalamic GT1-1 cells. The current study shows that the melanocortinergic system interacts with insulin signaling via novel effects on INK activity. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：1098 / 1104

页数：7

共 37 条

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