Glucagon-like peptide-1 secretion is influenced by perfusate glucose concentration and by a feedback mechanism involving somatostatin in isolated perfused porcine ileum

TY - JOUR

T1 - Glucagon-like peptide-1 secretion is influenced by perfusate glucose concentration and by a feedback mechanism involving somatostatin in isolated perfused porcine ileum

AU - Hansen, Lene

AU - Hartmann, Bolette

AU - Mineo, Hitoshi

AU - Holst, Jens Juul

PY - 2004/4/15

Y1 - 2004/4/15

N2 - 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.

AB - 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.

KW - Animals

KW - Feedback, Physiological

KW - Gastric Inhibitory Polypeptide

KW - Gastrointestinal Motility

KW - Glucagon

KW - Glucagon-Like Peptide 1

KW - Glucagon-Like Peptide 2

KW - Glucose

KW - Ileum

KW - In Vitro Techniques

KW - Insulin

KW - Peptide Fragments

KW - Peptide YY

KW - Peptides

KW - Perfusion

KW - Pressure

KW - Protein Precursors

KW - Somatostatin

KW - Swine

U2 - 10.1016/j.regpep.2003.10.021

DO - 10.1016/j.regpep.2003.10.021

M3 - Journal article

C2 - 14759551

SN - 0167-0115

VL - 118

SP - 11

EP - 18

JO - Regulatory Peptides

JF - Regulatory Peptides

IS - 1-2

ER -