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Taste signaling elements expressed in gut enteroendocrine cells regulate nutrient-responsive secretion of gut hormones^1,2,3,4

¹ From the Department of Neuroscience, Mount Sinai School of Medicine, New York, NY.

² Presented at the "100th Anniversary Symposium of Umami Discovery: The Roles of Glutamate in Taste, Gastrointestinal Function, Metabolism, and Physiology," held in Tokyo, Japan, 10–13 September 2008.

³ Supported in part by NIH grant DC03055 to RFM.

⁴ Address correspondence to RF Margolskee, Department of Neuroscience, Mount Sinai School of Medicine, 1425 Madison Avenue, Box 1065, New York, NY 10029. E-mail: robert.margolskee{at}mssm.edu.

Many of the receptors and downstream signaling elements involved in taste detection and transduction are also expressed in enteroendocrine cells where they underlie the chemosensory functions of the gut. In one well-known example of gastrointestinal chemosensation (the "incretin effect"), it is known that glucose that is given orally, but not systemically, induces secretion of glucagon-like peptide 1 and glucose-dependent insulinotropic peptide (the incretin hormones), which in turn regulate appetite, insulin secretion, and gut motility. Duodenal L cells express sweet taste receptors, the taste G protein gustducin, and several other taste transduction elements. Knockout mice that lack gustducin or the sweet taste receptor subunit T1r3 have deficiencies in secretion of glucagon-like peptide 1 and glucose-dependent insulinotropic peptide and in the regulation of plasma concentrations of insulin and glucose in response to orally ingested carbohydrate—ie, their incretin effect is dysfunctional. Isolated small intestine and intestinal villi from gustducin null mice displayed markedly defective glucagon-like peptide 1 secretion in response to glucose, indicating that this is a local circuit of sugar detection by intestinal cells followed by hormone secretion from these same cells. Modulating hormone secretion from gut "taste cells" may provide novel treatments for obesity, diabetes, and malabsorption syndromes.

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