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 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.
Kim Chung
Le Thi
le T
Department of Nutrition and Metabolism, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
Hosaka
Toshio
T
Yoshida
Masaki
M
Harada
Nagakatsu
N
Sakaue
Hiroshi
H
Sakai
Tohru
T
Nakaya
Yutaka
Y
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D054392:Adipokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D000067757:Glucagon-Like Peptide-1 Receptor; D007249:Inflammation / Q000378:metabolism; D007333:Insulin Resistance; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D010455:Peptides / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018027:Receptors, Glucagon / Q000819:agonists*; D013449:Sulfonamides / Q000494:pharmacology; D014688:Venoms / Q000494:pharmacology*
D054392:Adipokines; D052242:Adiponectin; C499919:Adipoq protein, mouse; C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D007546:Isoquinolines; D010455:Peptides; D010726:Phosphodiesterase Inhibitors; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D018027:Receptors, Glucagon; D013449:Sulfonamides; D014688:Venoms; D005576:Colforsin; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D015056:1-Methyl-3-isobutylxanthine