Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1
Hyeung-Jin Jang, Zaza Kokrashvili, Michael J Theodorakis, Olga D Carlson, Byung-Joon Kim, Jie Zhou, Hyeon Ho Kim, Xiangru Xu, Sic L Chan, Magdalena Juhaszova, Michel Bernier, Bedrich Mosinger, Robert F Margolskee, Josephine M Egan, Hyeung-Jin Jang, Zaza Kokrashvili, Michael J Theodorakis, Olga D Carlson, Byung-Joon Kim, Jie Zhou, Hyeon Ho Kim, Xiangru Xu, Sic L Chan, Magdalena Juhaszova, Michel Bernier, Bedrich Mosinger, Robert F Margolskee, Josephine M Egan
Abstract
Glucagon-like peptide-1 (GLP-1), released from gut endocrine L cells in response to glucose, regulates appetite, insulin secretion, and gut motility. How glucose given orally, but not systemically, induces GLP-1 secretion is unknown. We show that human duodenal L cells express sweet taste receptors, the taste G protein gustducin, and several other taste transduction elements. Mouse intestinal L cells also express alpha-gustducin. Ingestion of glucose by alpha-gustducin null mice revealed deficiencies in secretion of GLP-1 and the regulation of plasma insulin and glucose. Isolated small bowel and intestinal villi from alpha-gustducin null mice showed markedly defective GLP-1 secretion in response to glucose. The human L cell line NCI-H716 expresses alpha-gustducin, taste receptors, and several other taste signaling elements. GLP-1 release from NCI-H716 cells was promoted by sugars and the noncaloric sweetener sucralose, and blocked by the sweet receptor antagonist lactisole or siRNA for alpha-gustducin. We conclude that L cells of the gut "taste" glucose through the same mechanisms used by taste cells of the tongue. Modulating GLP-1 secretion in gut "taste cells" may provide an important treatment for obesity, diabetes and abnormal gut motility.
Conflict of interest statement
Conflict of interest statement: Dr. Margolskee has a personal financial interest in the form of stock ownership in the Redpoint Bio company, receives consulting fees from the Redpoint Bio company, and is an inventor on patents and patent applications which have been licensed to the Redpoint Bio company.
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Source: PubMed