Muscarinic Receptors Control Postprandial Release of Glucagon-Like peptide-1: In Vivo and in Vitro Studies in Rats

Endocrinology. 2002 Jun;143(6):2420-6. doi: 10.1210/endo.143.6.8840.

Abstract

Plasma levels of glucagon-like peptide-1 (GLP-1) rise rapidly after nutrient ingestion through an indirect mechanism triggered from the proximal intestine and involving the vagus nerve that stimulates the L cell in the distal gut. The role of muscarinic receptors in this pathway was thus investigated using the anesthetized rat and fetal rat intestinal cells (FRIC) in culture. GLP-1 secretion from the distal gut increased 5-fold after 3 ml corn oil were placed into the proximal duodenum (P < 0.001). Atropine (a nonspecific muscarinic receptor antagonist) completely inhibited fat-induced GLP-1 secretion in vivo (P < 0.01). Pirenzepine (an M1 muscarinic receptor antagonist) also inhibited fat-induced GLP-1 secretion in vivo, by 91 +/- 6% (P < 0.01). Gallamine (an M2 muscarinic receptor antagonist) and 4-diphenylacetoxy-N-methylpiperidine (an M3 muscarinic receptor antagonist) had no effect. Incubating FRIC cultures with bethanechol (a muscarinic receptor agonist) stimulated GLP-1 secretion to 200 +/- 22% of control (P < 0.01). Pirenzepine and gallamine significantly inhibited bethanechol-stimulated GLP-1 secretion, by 96 +/- 12% and 98 +/- 8%, respectively (P < 0.01). Unexpectedly, 4-diphenylacetoxy-N-methylpiperidine stimulated GLP-1 secretion by FRIC cells, to 324 +/- 52% of the control value (P < 0.01). Double immunofluorescent staining using GLP-1 and M1, M2, and M3 muscarinic receptor antibodies showed expression of the three subtypes of muscarinic receptors by the L cells in rat ileal sections and FRIC cultures. These results demonstrate the role of M1 muscarinic receptors expressed by L cells in the control of postprandial secretion of GLP-1. M2 muscarinic receptors also seem to play a role in controlling GLP-1 secretion by fetal, but not adult, L cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthesia
  • Animals
  • Cell Line
  • Cells, Cultured
  • Fluorescent Antibody Technique, Indirect
  • Glucagon / blood
  • Glucagon / metabolism*
  • Glucagon-Like Peptide 1
  • Ileum / cytology
  • Ileum / innervation
  • Ileum / metabolism
  • Immunohistochemistry
  • Male
  • Nerve Fibers / physiology
  • Peptide Fragments / blood
  • Peptide Fragments / metabolism*
  • Postprandial Period / physiology*
  • Protein Precursors / blood
  • Protein Precursors / metabolism*
  • Rats
  • Rats, Wistar
  • Receptors, Muscarinic / metabolism*

Substances

  • Peptide Fragments
  • Protein Precursors
  • Receptors, Muscarinic
  • Glucagon-Like Peptide 1
  • Glucagon