Serotonin receptor HTR4 as a counter actor of lipid-induced increases of serum glucagon-like peptide-1 levels
- PDF / 132,182 Bytes
- 2 Pages / 595.276 x 790.866 pts Page_size
- 70 Downloads / 134 Views
COMMENTARY
Serotonin receptor HTR4 as a counter actor of lipid-induced increases of serum glucagon-like peptide-1 levels Andreas Breit 1 & Thomas Gudermann 1 Received: 7 August 2020 / Revised: 7 August 2020 / Accepted: 14 August 2020 # The Author(s) 2020
In this issue of Pflügers Archiv—European Journal of Physiology, Okumura et al. present a new association between the serotonin and the GLP-1 system which, in turn, impacts serum insulin levels. In detail, they show a link between HTR4 activity in GLP-1 and PYY positive murine ileal epithelial cells and plasma levels of GLP-1 in mice. They first performed immunofluorescence staining to analyze HTR expression in murine ileum and colon. They found significant expression of HTR2A, HTR2B, and HTR4 expression in epithelial cells of both tissues. Interestingly, in the ileum, HTR4 was found in enteroendocrine (EE) L cells, a group of EE cells in the small intestine, which are also positive for GLP-1 and PYY as well as for serotonin (5-HT) expression. To validate these data, the authors also isolated small intestinal crypts from mice and cultured the dissociated cells. Here they could confirm that HTR4 positive cells co-express GLP-1 and PYY. These observations lead to the reasonable assumption that HTR4 signaling might affect GLP-1 and/or PYY release from these enteroendocrine L cells. In order to determine a potential association between HTR4 signaling and GLP-1 release, the authors monitored plasma GLP-1 levels from mice treated either intraperitoneally or intragastrically with the established selective HTR4 agonist tegaserod. Under these “basal conditions,” no effects of the HTR4 agonist on serum GLP-1 levels were detectable. However, when lipid-induced increase of serum GLP-1 levels was mimicked by administration of socalled Intralipos, a soybean oil emulsion, intragastric
This article is a commentary to the original article https://doi.org/10.1007/ s00424-020-02453-7 * Andreas Breit [email protected] 1
Walther Straub Institute of Pharmacology and Toxicology, Medical Faculty, LMU Munich, Goethestrasse 33, 80336 Munich, Germany
administration of tegasteron 30 min before significantly reduced Intralipos-induced increases of serum GLP-1 levels. This effect was inhibited by the co-administration of the HTR4 antagonist RS39604 confirming the importance of HTR4 signaling for this process. Interestingly, intraperitoneal administration of tegasteron failed to block Intralipos-induced increases of serum GLP-1 levels. GLP-1 together with the gastric inhibitory polypeptide (GIP) are the two principle incretin hormones. Incretins are metabolic hormones that are released after eating and decreased blood glucose by augmentation of insulin secretion from pancreatic beta cells of the islets of Langerhans. Incretins are responsible for the observation that intravenous injection of glucose leads to less insulin secretion compared with oral glucose administration: the so-called incretin effect. Given the strong interaction between the GLP-1 system and insulin/glucose
Data Loading...
