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  Neurotensin Is Coexpressed, Coreleased, and Acts Together With GLP-1 and PYY in Enteroendocrine Control of Metabolism

Grunddal, K. V., Ratner, C. F., Svendsen, B., Sommer, F., Engelstoft, M. S., Madsen, A. N., et al. (2016). Neurotensin Is Coexpressed, Coreleased, and Acts Together With GLP-1 and PYY in Enteroendocrine Control of Metabolism. ENDOCRINOLOGY, 157(1), 176-194. doi:10.1210/en.2015-1600.

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 Urheber:
Grunddal, Kaare V., Autor
Ratner, Cecilia F., Autor
Svendsen, Berit, Autor
Sommer, Felix, Autor
Engelstoft, Maja S., Autor
Madsen, Andreas N., Autor
Pedersen, Jens, Autor
Nohr, Mark K., Autor
Egerod, Kristoffer L., Autor
Nawrocki, Andrea R., Autor
Kowalski, Timothy, Autor
Howard, Andrew D., Autor
Poulsen, Steen Seier, Autor
Offermanns, Stefan1, Autor           
Backhed, Fredrik, Autor
Holst, Jens J., Autor
Holst, Birgitte, Autor
Schwartz, Thue W., Autor
Affiliations:
1Pharmacology, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591696              

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Schlagwörter: GLUCAGON-LIKE PEPTIDE-1; DEPENDENT INSULINOTROPIC POLYPEPTIDE; PANCREATIC ENDOCRINE RESPONSES; PROXIMAL SMALL-INTESTINE; GASTRIC-ACID SECRETION; CENTRAL-NERVOUS-SYSTEM; FOOD-INTAKE; CELL-DIFFERENTIATION; ENERGY-BALANCE; BINDING-SITESEndocrinology & Metabolism;
 Zusammenfassung: The 2 gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are well known to be coexpressed, costored, and released together to coact in the control of key metabolic target organs. However, recently, it became clear that several other gut hormones can be coexpressed in the intestinal-specific lineage of enteroendocrine cells. Here, we focus on the anatomical and functional consequences of the coexpression of neurotensin with GLP-1 and PYY in the distal small intestine. Fluorescence-activated cell sorting analysis, laser capture, and triple staining demonstrated that GLP-1 cells in the crypts become increasingly multihormonal, ie, coexpressing PYY and neurotensin as they move up the villus. Proglucagon promoter and pertussis toxin receptor-driven cell ablation and reappearance studies indicated that although all the cells die, the GLP-1 cells reappear more quickly than PYY- and neurotensin-positive cells. High-resolution confocal fluorescence microscopy demonstrated that neurotensin is stored in secretory granules distinct from GLP-1 and PYY storing granules. Nevertheless, the 3 peptides were cosecreted from both perfused small intestines and colonic crypt cultures in response to a series of metabolite, neuropeptide, and hormonal stimuli. Importantly, neurotensin acts synergistically, ie, more than additively together with GLP-1 and PYY to decrease palatable food intake and inhibit gastric emptying, but affects glucose homeostasis in a more complex manner. Thus, neurotensin is a major gut hormone deeply integrated with GLP-1 and PYY, which should be taken into account when exploiting the enteroendocrine regulation of metabolism pharmacologically.

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Sprache(n): eng - English
 Datum: 2016
 Publikationsstatus: Erschienen
 Seiten: 19
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: -
 Identifikatoren: ISI: 000369962600023
DOI: 10.1210/en.2015-1600
 Art des Abschluß: -

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Titel: ENDOCRINOLOGY
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA : ENDOCRINE SOC
Seiten: - Band / Heft: 157 (1) Artikelnummer: - Start- / Endseite: 176 - 194 Identifikator: ISSN: 0013-7227