T1r3 and alpha-Gustducin in Gut Regulate Secretion of Glucagon-like Peptide-1

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that underlies the augmented insulin release from the pancreas in response to glucose in the gut lumen more than to intravenous injected glucose (the incretin effect). GLP-1, found in enteroendocrine L cells of the gut, regulates appetite and gut motility and is released from L cells in response to glucose. GLP-1-expressing duodenal L cells also express T1r taste receptors, alpha-gustducin, and many other taste transduction elements. Knockout mice lacking alpha-gustducin or T1r3 have deficiencies in secretion of GLP-1 and in the regulation of plasma levels of insulin and glucose. Gut-expressed taste-signaling elements underlie multiple chemosensory functions of the gut including the incretin effect. Modulating hormone secretion from gut taste cells may provide novel treatments for obesity, diabetes, and malabsorption.