Hyeung-Jin Jang1, Zaza Kokrashvili2,3, Michael J. Theodorakis4, Olga D. Carlson4, Byung-Joon Kim4, Jie Zhou4, Hyeon Ho Kim4,5, X.Z. Shawn Xu4, Sic L. Chan4, Magdalena Juhaszova4, Michel Bernier4, B Mosinger2,3,6, Robert F. Margolskee2,3, Josephine M. Egan4
1National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA
2Department of Neuroscience,
3Department of Neuroscience, Mount Sinai School of Medicine, 1425 Madison Avenue, Box 1065, New York, NY 10029
4*National Institute on Aging/National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224; and
5University of Florida, Gainesville, FL
6National Institute on Aging/National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224;
Tóm tắt
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 α-gustducin. Ingestion of glucose by α-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 α-gustducin null mice showed markedly defective GLP-1 secretion in response to glucose. The human L cell line NCI-H716 expresses α-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 α-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.
