The effects of duodenal peptides on glucagon-like peptide-1 secretion from the ileum. A duodeno--ileal loop?
Secretion of the gut hormone glucagon-like peptide-1 (GLP-1) is stimulated by meal ingestion. The response is rapid, suggesting a stimulatory pathway elicited from the upper gastrointestinal area. In pigs, we have been unable to demonstrate a neural stimulatory pathway, but GLP-1 secretion is regulated by local somatostatin secretion. In search for an endocrine pathway, we studied the effect of a range of concentrations of cholecystokinin octapeptide (26-33) (CCK 8), gastric inhibitory peptide 1-42 (GIP), secretin, motilin, calcitonin gene-related peptide (CGRP), and the modified amino acid, 5-hydroxytryptamine (serotonin, 5-HT) on GLP-1 and somatostatin release from isolated perfused segments of porcine ileum.GLP-1 secretion was stimulated by 1 nM CCK 8 and 10 nM GIP, but suppressed by 1 nM motilin and 1 microM 5-HT. Secretin and CGRP had no effect. Somatostatin secretion was stimulated by CCK 8 at 1 and 10 nM, by GIP at 1 and 10 nM and by 10 nM CGRP. Secretin, 5-HT and motilin had no effect on somatostatin secretion. We conclude that CCK 8 and GIP 1-42 stimulated GLP-1 secretion, but only in concentrations greatly exceeding normal postprandial concentrations. Thus, we find it unlikely that endocrine agents from the duodenum regulate GLP-1 secretion in pigs.
Hansen
Lene
L
Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 N, Copenhagen, Denmark. holst@mfi.ku.dk
Holst
Jens J
JJ
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D010478:Chemotherapy, Cancer, Regional Perfusion; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology; D005768:Gastrointestinal Hormones / Q000494:pharmacology*; D005934:Glucagon / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1; D007082:Ileum / Q000187:drug effects / Q000378:metabolism*; D009037:Motilin / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism*; D019518:Postprandial Period / Q000502:physiology; D011498:Protein Precursors / Q000378:metabolism*; D012844:Sincalide / Q000031:analogs & derivatives* / Q000494:pharmacology; D013552:Swine
D005768:Gastrointestinal Hormones; D010446:Peptide Fragments; D011498:Protein Precursors; D009037:Motilin; D005749:Gastric Inhibitory Polypeptide; C044201:cholecystokinin (26-33); D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D015740:Calcitonin Gene-Related Peptide; D012844:Sincalide