Tang, Cong, Ksiazek, Iwona, Siccardi, Noemie, Gapp, Berangere, Weber, Delphine, Wirsching, Johann, Beck, Valerie, Reist, Matthias, Gaudet, Laurent, Beibel, Martin, Roma, Guglielmo, Gubser Keller, Caroline and Bassilana, Frederic (2019) UTS2B defines a novel enteroendocrine cell population and regulates GLP-1 secretion through SSTR5 in male mice. Endocrinology. ISSN 1945-7170

Abstract

The gut-pancreas axis plays a key role in the regulation of glucose homeostasis and may be therapeutically exploited to treat not only type II diabetes, but also hypoglycemia and hyperinsulinemia. We identify a novel enteroendocrine cell type expressing the peptide hormone urotensin 2B (UTS2B). UTS2B inhibits glucagon like peptide-1 (GLP-1) secretion in mouse intestinal crypts and organoids, not by signaling through its cognate receptor UTS2R but through the activation of the somatostatin receptor 5 (SSTR5). Circulating UTS2B concentrations in mice are physiologically regulated during starvation, further linking this peptide hormone to metabolism. Furthermore, administration of UTS2B to starved mice demonstrates that it is capable of regulating blood glucose and plasma concentrations of GLP-1 and insulin in vivo. Altogether, our results identify a novel cellular source of UTS2B in the gut, which acts in a paracrine manner to regulate GLP-1 secretion through SSTR5.These findings uncover a fine-tuning mechanism mediated by a ligand-receptor pair in the regulation of gut hormone secretion, which can be potentially exploited to correct metabolic unbalance caused by over-activation of the gut-pancreas axis.

Item Type:	Article
Date Deposited:	11 Oct 2019 00:45
Last Modified:	11 Oct 2019 00:45
URI:	https://oak.novartis.com/id/eprint/37005