Abstract
Gastrin and cholecystokinin (CCK) are hormones released from endocrine cells in the antral stomach (gastrin), the duodenum, and the jejunum (CCK). Recent reports, based on secretion experiments in an enteroendocrine cell line (NCI‐H716) and gastrin receptor expression in proglucagon‐expressing cells from the rat colon, suggested that gastrin could be a regulator of glucagon‐like peptide‐1 (GLP‐1) secretion. To investigate these findings, we studied the acute effects of CCK‐8 (a CCK1/CCK2 (gastrin) receptor agonist) and gastrin‐17 (a CCK2(gastrin) receptor agonist) in robust ex vivo models: the isolated perfused rat small intestine and the isolated perfused rat colon. Small intestines from Wistar rats (n = 6), were perfused intraarterially over 80 min. During the perfusion, CCK (1 nmol/L) and gastrin (1 nmol/L) were infused over 10‐min periods separated by washout/baseline periods. Colons from Wistar rats (n = 6) were perfused intraarterially over 100 min. During the perfusion, CCK (1 nmol/L), vasoactive intestinal peptide (VIP) (10 nmol/L), and glucose‐dependent insulinotropic polypeptide (GIP) (1 nmol/L) were infused over 10‐min periods separated by washout/baseline periods. In the perfused rat small intestines neither CCK nor gastrin stimulated the release of GLP‐1 or neurotensin. In the perfused rat colon, neither CCK or VIP stimulated GLP‐1 or peptide YY (PYY) release, but GIP stimulated both GLP‐1 and PYY release. In both sets of experiments, bombesin, a gastrin‐releasing peptide analog, served as a positive control. Our findings do not support the suggestion that gastrin or CCK participate in the acute regulation of intestinal GLP‐1 secretion, but that GIP may play a role in the regulation of hormone secretion from the colon.
Highlights
Gastrin and cholecystokinin (CCK) are gastrointestinal hormones released from endocrine cells in the antral stomach and the duodenum and jejunum (CCK) (Rehfeld, 1998)
It has been suggested, based on gastrin receptor expression in a human enteroendocrine cell line (NCIH716) and in proglucagon-expressing cells harvested from rat colon tissue, that gastrin, released from the proximal gastrointestinal tract is involved in the regulation of the more distal gut hormone glucagon-like peptide-1 (GLP-1) (Cao, Cao, & Liu, 2015)
To investigate the recent findings regarding gastrin-stimulated GLP-1 secretion(Cao et al, 2015), we tested whether gastrin and CCK at supra-physiological levels would elicit secretion of GLP-1, peptide YY (PYY), and neurotensin, gut peptides released from different enteroendocrine cell subpopulations (L-cells (GLP-1 and PYY, small intestine and colon) and N-cells, respectively)
Summary
CBC was supported by PhD scholarships from the Danish Diabetes Academy and the Lundbeck Foundation. The study was supported by an unrestricted grant from the NNF Center for Basic Metabolic Research – an independent research institution based at the University of Copenhagen and by the European Research Council (grant no. 695069) to JJH. SV was supported by Doctor Sofus Carl Emil Friis and wife Olga Doris Friis’ Legacy (Læge Sofus Carl Emil Friis og Hustru Olga Doris Friis legat) and the Independent Research Fund Denmark.
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