Muscarinic receptors control postprandial release of glucagon-like peptide-1: in vivo and in vitro studies in rats.
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.
Anini
Younes
Y
Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
Hansotia
Tanya
T
Brubaker
Patricia L
PL
D000758:Anesthesia; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D019084:Fluorescent Antibody Technique, Indirect; D005934:Glucagon / Q000097:blood / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1; D007082:Ileum / Q000166:cytology / Q000294:innervation / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009412:Nerve Fibers / Q000502:physiology; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism*; D019518:Postprandial Period / Q000502:physiology*; D011498:Protein Precursors / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism*
D010446:Peptide Fragments; D011498:Protein Precursors; D011976:Receptors, Muscarinic; D052216:Glucagon-Like Peptide 1; D005934:Glucagon