Alpha7 Nicotinic Acetylcholine Receptor Regulates the Function and Viability of Enteroendocrine L Cells In Vitro.

Alpha7 Nicotinic Acetylcholine Receptor Regulates the Function and Viability of Enteroendocrine L Cells In Vitro. Endocrinology. 2018 Jul 09;: Authors: Wang D, Meng Q, Leech CA, Yepuri N, Zhang L, Holz GG, Wang C, Cooney RN Abstract Enteroendocrine L cells secrete the incretin hormone glucagon-like peptide-1 (GLP-1) and they also express the α7 nicotinic acetylcholine receptor (α7nAChR) that might regulate GLP-1 secretion. Here, GTS-21, a selective α7nAChR agonist, was used to examine the impact of α7nAChR activation in L-cell lines, mouse intestinal primary cell cultures, and C57BL/6 mice. GTS-21 stimulated GLP-1 secretion in vitro and this effect was attenuated by an α7nAChR antagonist or by α7nAChR-specific siRNA. Under in vitro cell culture conditions of glucotoxicity, GTS-21 restored GLP-1 secretion and improved L-cell viability, while also acting in vivo to raise levels of circulating GLP-1 in mice. To assess potential signaling mechanisms underlying these actions of GTS-21, we first monitored Ca2+, cAMP, and PI3K activity. As expected for a GLP-1 secretagogue promoting Ca2+ influx through α7nAChR cation channels, [Ca2+]i increased in response to GTS-21, but [cAMP]i was unchanged. Surprisingly, pharmacological inhibition of growth factor signaling pathways revealed that GTS-21 also acts on the PI3K-Akt-mTOR pathway to promote L-cell viability. Moreover, the Ca2+ chelator BAPTA-AM counteracted GTS-21-stimulated PI3K activ...
Source: Endocrinology - Category: Endocrinology Authors: Tags: Endocrinology Source Type: research