An Analysis of Cosecretion and Coexpression of Gut Hormones From Male Rat Proximal and Distal Small Intestine

TY - JOUR

T1 - An Analysis of Cosecretion and Coexpression of Gut Hormones From Male Rat Proximal and Distal Small Intestine

AU - Svendsen, Berit

AU - Pedersen, Jens

AU - Albrechtsen, Nicolai Jacob Wewer

AU - Hartmann, Bolette

AU - Toräng, Signe

AU - Rehfeld, Jens F

AU - Seier Poulsen, Steen

AU - Holst, Jens Juul

PY - 2015/3/1

Y1 - 2015/3/1

N2 - 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.Westudied the coexpression and cosecretion of gut hormones in separate segments of rat small intestine.Wemeasured secretion of glucagon-like peptide-1 (GLP-1), peptideYY(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 hormonesresponded to all three stimuli (butnoGIP response to bombesin). GLP-1 secretionwassimilar 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.

AB - 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.Westudied the coexpression and cosecretion of gut hormones in separate segments of rat small intestine.Wemeasured secretion of glucagon-like peptide-1 (GLP-1), peptideYY(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 hormonesresponded to all three stimuli (butnoGIP response to bombesin). GLP-1 secretionwassimilar 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.

U2 - 10.1210/en.2014-1710

DO - 10.1210/en.2014-1710

M3 - Journal article

C2 - 25535831

SN - 0013-7227

VL - 156

SP - 847

EP - 857

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 3

M1 - en20141710

ER -