Exendin-4, a GLP-1 receptor agonist, directly induces adiponectin expression through protein kinase A pathway and prevents inflammatory adipokine expression

被引:168
作者
Chung, Le Thi Kim [1 ]
Hosaka, Toshio [2 ]
Yoshida, Masaki [1 ]
Harada, Nagakatsu [1 ]
Sakaue, Hiroshi [1 ]
Sakai, Tohru [2 ]
Nakaya, Yutaka [1 ]
机构
[1] Univ Tokushima, Grad Sch, Inst Hlth Biosci, Dept Nutr & Metab, Tokushima 7708503, Japan
[2] Univ Tokushima, Grad Sch, Inst Hlth Biosci, Dept Publ Hlth & Appl Nutr, Tokushima 7708503, Japan
关键词
Exendin-4; Adiponectin; GLP-1; GLUCAGON-LIKE PEPTIDE-1; PANCREATIC BETA-CELL; TUMOR-NECROSIS-FACTOR; INSULIN-RESISTANCE; 3T3-L1; ADIPOCYTES; SIGNAL-TRANSDUCTION; GLUCOSE-TRANSPORT; GENE-EXPRESSION; ADIPOSE-TISSUE; INTERLEUKIN-6;
D O I
10.1016/j.bbrc.2009.10.015
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Exendin-4 (Ex-4) is a glucagon-like peptide-1 receptor (GLP-1R) agonist that has been used as a drug injected subcutaneously for treatment of type 2 diabetes. Many studies have revealed molecular targets of Ex-4, but its influence on adipokines has not been determined. Our study showed that Ex-4 induced secretion of adiponectin into the culture medium of 3T3-L1 adipocytes. This effect of Ex-4 is due to increased adiponectin mRNA level through the GLP-1R. Both forskolin and 3-isobutyl-1-methylxanthine (IBMX), which may finally elevate cyclic adenosine monophosphate (cAMP) concentration, prevented the induction of adiponectin expression by Ex-4. Moreover, H89, a protein kinase A inhibitor, blocked the effect of Ex-4 on adiponectin. On the other hand, Ex-4 decreased the mRNA levels of inflammatory adipokines. The results indicate that Ex-4 directly promotes adiponectin secretion via the protein kinase A pathway in 3T3-L1 adipocytes and may ameliorate insulin resistance. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:613 / 618
页数:6
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