Novel signal transduction and peptide specificity of glucagon-like peptide receptor in 3T3-L1 adipocytes.
Glucagon-like peptide-1 (7-36) amide (GLP-1), in addition to its well known effect of enhancing glucose-mediated insulin release, has been shown to have insulinomimetic effects and to enhance insulin-mediated glucose uptake and lipid synthesis in 3T3-L1 adipocytes. To elucidate the mechanisms of GLP-1 action in these cells, we studied the signal transduction and peptide specificity of the GLP-1 response. In 3T3-L1 adipocytes, GLP-1 caused a decrease in intracellular cAMP levels which is the opposite to the response observed in pancreatic beta cells in response to the same peptide. In 3T3-L1 adipocytes, free intracellular calcium was not modified by GLP-1. Peptide specificity was examined to help determine if a different GLP receptor isoform was expressed in 3T3-L1 adipocytes vs. beta cells. Peptides with partial homology to GLP-1 such as GLP-2, GLP-1 (1-36), and glucagon all lowered cAMP levels in 3T3-L1 adipocytes. In addition, an antagonist of pancreatic GLP-1 receptor, exendin-4 (9-39), acted as an agonist to decrease cAMP levels in 3T3-L1 adipocytes as did exendin-4 (1-39), a known agonist for the pancreatic GLP-1 receptor. Binding studies using 125I-GLP-1 also suggest that pancreatic GLP-1 receptor isoform is not responsible for the effect of GLP-1 and related peptides in 3T3-L1 adipocytes. Based on these results, we propose that the major form of the GLP receptor in 3T3-L1 adipocytes is functionally different from the pancreatic GLP-1 receptor.
Montrose-Rafizadeh
C
C
Gerontology Research Center, National Institute on Aging, NIH, Baltimore, Maryland 21224-2780, USA. chahrzad@vax.grc.nia.nih.gov
Yang
H
H
Wang
Y
Y
Roth
J
J
Montrose
M H
MH
Adams
L G
LG
D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D000077270:Exenatide; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D004763:Glucagon-Like Peptides; D008066:Lipolysis / Q000187:drug effects; D051379:Mice; D010446:Peptide Fragments; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism; D018027:Receptors, Glucagon / Q000378:metabolism*; D015398:Signal Transduction; D014688:Venoms
C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D010455:Peptides; D011964:Receptors, Gastrointestinal Hormone; D018027:Receptors, Glucagon; D014688:Venoms; C055453:glucagon-like peptide 1 (7-36)amide; D005749:Gastric Inhibitory Polypeptide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000077270:Exenatide; C041086:gastric inhibitory polypeptide receptor; D000242:Cyclic AMP; D002118:Calcium