Novel signal transduction and peptide specificity of glucagon-like peptide receptor in 3T3-L1 adipocytes

J Cell Physiol. 1997 Sep;172(3):275-83. doi: 10.1002/(SICI)1097-4652(199709)172:3<275::AID-JCP1>3.0.CO;2-L.


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.

Publication types

  • Comparative Study

MeSH terms

  • 3T3 Cells
  • Adipocytes / metabolism*
  • Animals
  • Binding, Competitive
  • CHO Cells
  • Calcium / metabolism
  • Cricetinae
  • Cyclic AMP / metabolism
  • Exenatide
  • Gastric Inhibitory Polypeptide / pharmacology
  • Glucagon / pharmacology
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptide-1 Receptor
  • Glucagon-Like Peptides
  • Lipolysis / drug effects
  • Mice
  • Peptide Fragments*
  • Peptides / metabolism
  • Peptides / pharmacology*
  • Receptors, Gastrointestinal Hormone / metabolism
  • Receptors, Glucagon / metabolism*
  • Signal Transduction*
  • Venoms*


  • Glp1r protein, mouse
  • Glucagon-Like Peptide-1 Receptor
  • Peptide Fragments
  • Peptides
  • Receptors, Gastrointestinal Hormone
  • Receptors, Glucagon
  • Venoms
  • glucagon-like peptide 1 (7-36)amide
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • Glucagon
  • Exenatide
  • gastric inhibitory polypeptide receptor
  • Cyclic AMP
  • Calcium