Glucagon-like peptide-1 secretion is influenced by perfusate glucose concentration and by a feedback mechanism involving somatostatin in isolated perfused porcine ileum.
Glucagon-like peptide-1 (GLP-1) is released from intestinal L-cells in response to ingestion of meals. The mechanisms regulating its secretion are not clear, but local somatostatin (SS) restrains GLP-1 secretion. We investigated feedback and substrate regulation of GLP-1 and SS secretion, using isolated perfused porcine ileum (n=17). Effluents were measured for GLP-1 and SS. Perfusion pressure and motility were recorded. Investigated parameters included spontaneous fluctuations, changes in perfusate glucose concentrations (3.5, 5, 11 mM) and addition of insulin (1 nM). We also investigated the effect of proglucagon products, glucagon (10 nM), GLP-1 and GLP-2 (0.1, 1, and 10 nM) on GLP-1 and SS secretion, as well as on glucagon-like peptide-2 (GLP-2), peptide YY (PYY) and GIP secretion, all possible product of L-cells or neighbour cells. Perfusate glucose concentration dose-dependently stimulated GLP-1 secretion (p=0.011). Insulin had no effect. Glucagon weakly stimulated GIP secretion. GLP-1 stimulated SS secretion and motor activity, but inhibited GLP-2, GIP and PYY secretion and perfusion pressure. GLP-2 weakly stimulated SS secretion. We conclude (a) that GLP-1 secretion is influenced by perfusate glucose concentration and (b) that L-cell secretion is feedback regulated by GLP-1 itself, probably via paracrine SS activity.
Hansen
Lene
L
Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen, Denmark.
Hartmann
Bolette
B
Mineo
Hitoshi
H
Holst
Jens J
JJ
D000818:Animals; D025461:Feedback, Physiological / Q000502:physiology*; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D005934:Glucagon / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D052216:Glucagon-Like Peptide 1; D053767:Glucagon-Like Peptide 2; D005947:Glucose / Q000032:analysis / Q000502:physiology*; D007082:Ileum / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism* / Q000502:physiology; D019894:Peptide YY / Q000378:metabolism; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D010477:Perfusion; D011312:Pressure; D011498:Protein Precursors / Q000378:metabolism* / Q000502:physiology; D013004:Somatostatin / Q000378:metabolism* / Q000502:physiology; D013552:Swine
D053767:Glucagon-Like Peptide 2; D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D019894:Peptide YY; D013004:Somatostatin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose