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

Biochem Biophys Res Commun. 2009 Dec 18;390(3):613-8. doi: 10.1016/j.bbrc.2009.10.015. Epub 2009 Oct 20.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • 3T3-L1 Cells
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipokines / antagonists & inhibitors*
  • Adipokines / biosynthesis
  • Adiponectin / metabolism
  • Animals
  • Colforsin / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Exenatide
  • 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
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Messenger / biosynthesis
  • Receptors, Glucagon / agonists*
  • Sulfonamides / pharmacology
  • Venoms / pharmacology*

Substances

  • Adipokines
  • Adiponectin
  • Adipoq protein, mouse
  • Glp1r protein, mouse
  • Glucagon-Like Peptide-1 Receptor
  • Isoquinolines
  • Peptides
  • Phosphodiesterase Inhibitors
  • Protein Kinase Inhibitors
  • RNA, Messenger
  • Receptors, Glucagon
  • Sulfonamides
  • Venoms
  • Colforsin
  • Glucagon-Like Peptide 1
  • Exenatide
  • Cyclic AMP-Dependent Protein Kinases
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
  • 1-Methyl-3-isobutylxanthine