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

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 ind...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2009-12, Vol.390 (3), p.613-618
Main Authors: Kim Chung, Le Thi, Hosaka, Toshio, Yoshida, Masaki, Harada, Nagakatsu, Sakaue, Hiroshi, Sakai, Tohru, Nakaya, Yutaka
Format: Article
Language:English
Subjects:
1-Methyl-3-isobutylxanthine - pharmacology
3T3-L1 Cells
Adipocytes - drug effects
Adipocytes - metabolism
Adipokines - antagonists & inhibitors
Adipokines - biosynthesis
Adiponectin
Adiponectin - metabolism
Animals
Colforsin - pharmacology
Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors
Cyclic AMP-Dependent Protein Kinases - metabolism
Exendin-4
GLP-1
Glucagon-Like Peptide 1 - pharmacology
Glucagon-Like Peptide-1 Receptor
Inflammation - metabolism
Insulin Resistance
Isoquinolines - pharmacology
Mice
Peptides - pharmacology
Phosphodiesterase Inhibitors - pharmacology
Protein Kinase Inhibitors - pharmacology
Receptors, Glucagon - agonists
RNA, Messenger - antagonists & inhibitors
RNA, Messenger - biosynthesis
Sulfonamides - pharmacology
Venoms - pharmacology
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2009.10.015