title: An analysis of cosecretion and coexpression of gut hormones from male rat proximal and distal small intestine.
abstract: Gut endocrine cells are generally thought to have distinct localization and secretory products. Recent studies suggested that the cells are highly related and have potential to express more than one hormone. We studied the coexpression and cosecretion of gut hormones in separate segments of rat small intestine. We measured secretion of glucagon-like peptide-1 (GLP-1), peptide YY (PYY), neurotensin, glucose-dependent insulinotropic polypeptide (GIP), and cholecystokinin (CCK) from proximal and distal half of the small intestine, isolated from male rats and perfused ex vivo. Hormone secretion was stimulated by bombesin, the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, and peptones. Furthermore, tissue samples collected along the intestine were analyzed for expression, hormone content, and cell densities including colocalization. Most hormones responded to all three stimuli (but no GIP response to bombesin). GLP-1 secretion was similar from proximal and distal intestine, whereas PYY was secreted only from the distal half. CCK and GIP were mainly secreted proximally, whereas neurotensin was equally secreted from both parts. Cell densities, hormone concentrations, and expression patterns were generally parallel, with increasing values distally for GLP-1 and PYY, an exclusively proximal pattern for CCK, even distribution for neurotensin and GIP except for the most distal segments. PYY nearly always colocalized with GLP-1. Approximately 20% of GLP-1 cells colocalized with CCK and neurotensin, whereas GLP-1/GIP colocalization was rare. Our findings indicate that two L cell types exist, a proximal one secreting GLP-1 (and possibly CCK and neurotensin), and a distal one secreting GLP-1 and PYY. GIP seems to be secreted from cells that are not cosecreting other peptides.
authors.affiliation: Department of Biomedical Sciences (B.S., J.P., N.J.W.A., B.H., S.T., S.S.P., J.J.H.), Faculty of health Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research (B.S., J.P., N.J.W.A., B.H., S.T., S.S.P., J.J.H.), and Department of Clinical Biochemistry (J.F.R.), Rigshospitalet, University of Copenhagen, DK-2400 Copenhagen, Denmark.
authors.forename: Berit
authors.initials: B
authors.lastname: Svendsen
authors.forename: Jens
authors.initials: J
authors.lastname: Pedersen
authors.forename: Nicolai Jacob Wewer
authors.initials: NJ
authors.lastname: Albrechtsen
authors.forename: Bolette
authors.initials: B
authors.lastname: Hartmann
authors.forename: Signe
authors.initials: S
authors.lastname: Toräng
authors.forename: Jens F
authors.initials: JF
authors.lastname: Rehfeld
authors.forename: Steen Seier
authors.initials: SS
authors.lastname: Poulsen
authors.forename: Jens Juul
authors.initials: JJ
authors.lastname: Holst
mesh_terms: D000818:Animals; D000906:Antibodies; D002766:Cholecystokinin / Q000235:genetics / Q000378:metabolism*; D005749:Gastric Inhibitory Polypeptide / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009496:Neurotensin / Q000235:genetics / Q000378:metabolism*; D019894:Peptide YY / Q000235:genetics / Q000378:metabolism*; D010461:Peptones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000906:Antibodies; D010461:Peptones; D019894:Peptide YY; D009496:Neurotensin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D002766:Cholecystokinin