GLP-1 action in L6 myotubes is via a receptor different from the pancreatic GLP-1 receptor.
The incretin hormone glucagon-like peptide-1 (GLP-1)-(7-36) amide is best known for its antidiabetogenic actions mediated via a GLP-1 receptor present on pancreatic endocrine cells. To investigate the molecular mechanisms of GLP-1 action in muscle, we used cultured L6 myotubes. In L6 myotubes, GLP-1 enhanced insulin-stimulated glycogen synthesis by 140% while stimulating CO2 production and lactate formation by 150%. In the presence of IBMX, GLP-1 diminished cAMP levels to 83% of IBMX alone. In L6 myotubes transfected with pancreatic GLP-1 receptor, GLP-1 increased cAMP levels and inhibited glycogen synthesis by 60%. An antagonist of pancreatic GLP-1 receptor, exendin-4-(9-39), inhibited GLP-1-mediated glycogen synthesis in GLP-1 receptor-transfected L6 myotubes. However, in parental L6 myotubes, exendin-4-(9-39) and GLP-1-(1-36) amide, an inactive peptide on pancreatic GLP-1 receptor, displaced 125I-labeled GLP-1 binding and stimulated glycogen synthesis by 186 and 130%, respectively. These results suggest that the insulinomimetic effects of GLP-1 in L6 cells are likely to be mediated by a receptor that is different from the GLP-1 receptor found in the pancreas.
Yang
H
H
Laboratory of Clinical Physiology, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Egan
J M
JM
Wang
Y
Y
Moyes
C D
CD
Roth
J
J
Montrose
M H
MH
Montrose-Rafizadeh
C
C
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D006003:Glycogen / Q000096:biosynthesis*; D006019:Glycolysis / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D010179:Pancreas / Q000378:metabolism / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D011498:Protein Precursors / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D018027:Receptors, Glucagon / Q000096:biosynthesis / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D014688:Venoms / Q000494:pharmacology
C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D018027:Receptors, Glucagon; D011994:Recombinant Proteins; D014688:Venoms; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1; D002217:Carbachol; D006003:Glycogen; D005934:Glucagon; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine