title: Leptin suppresses sweet taste responses of enteroendocrine STC-1 cells.
abstract: Leptin is an important hormone that regulates food intake and energy homeostasis by acting on central and peripheral targets. In the gustatory system, leptin is known to selectively suppress sweet responses by inhibiting the activation of sweet sensitive taste cells. Sweet taste receptor (T1R2+T1R3) is also expressed in gut enteroendocrine cells and contributes to nutrient sensing, hormone release and glucose absorption. Because of the similarities in expression patterns between enteroendocrine and taste receptor cells, we hypothesized that they may also share similar mechanisms used to modify/regulate the sweet responsiveness of these cells by leptin. Here, we used mouse enteroendocrine cell line STC-1 and examined potential effect of leptin on Ca(2+) responses of STC-1 cells to various taste compounds. Ca(2+) responses to sweet compounds in STC-1 cells were suppressed by a rodent T1R3 inhibitor gurmarin, suggesting the involvement of T1R3-dependent receptors in detection of sweet compounds. Responses to sweet substances were suppressed by ⩾1ng/ml leptin without affecting responses to bitter, umami and salty compounds. This effect was inhibited by a leptin antagonist (mutant L39A/D40A/F41A) and by ATP gated K(+) (KATP) channel closer glibenclamide, suggesting that leptin affects sweet taste responses of enteroendocrine cells via activation of leptin receptor and KATP channel expressed in these cells. Moreover, leptin selectively inhibited sweet-induced but not bitter-induced glucagon-like peptide-1 (GLP-1) secretion from STC-1 cells. These results suggest that leptin modulates sweet taste responses of enteroendocrine cells to regulate nutrient sensing, hormone release and glucose absorption in the gut.
authors.affiliation: Section of Oral Neuroscience, Graduate School of Dental Sciences, Kyushu University, Fukuoka 812-8582, Japan; Monell Chemical Senses Center, Philadelphia, PA, United States.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Jyotaki
authors.affiliation: Section of Oral Neuroscience, Graduate School of Dental Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sanematsu
authors.affiliation: Section of Oral Neuroscience, Graduate School of Dental Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Noriatsu
authors.initials: N
authors.lastname: Shigemura
authors.affiliation: Section of Oral Neuroscience, Graduate School of Dental Sciences, Kyushu University, Fukuoka 812-8582, Japan; OBT Research Center, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Yoshida
authors.affiliation: Section of Oral Neuroscience, Graduate School of Dental Sciences, Kyushu University, Fukuoka 812-8582, Japan; Division of Sensory Physiology, Research and Development Center for Taste and Odor Sensing, Kyushu University, Fukuoka, Japan; Monell Chemical Senses Center, Philadelphia, PA, United States. Electronic address: yuninom@dent.kyushu-u.ac.jp.
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Ninomiya
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D019858:Enteroendocrine Cells / Q000187:drug effects / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D007150:Immunohistochemistry; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D020738:Leptin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D016133:Polymerase Chain Reaction; D026902:Potassium Channel Blockers / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D054411:Receptors, Leptin / Q000378:metabolism; D013649:Taste / Q000187:drug effects / Q000502:physiology*; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D054086:KATP Channels; D020738:Leptin; D026902:Potassium Channel Blockers; D043562:Receptors, G-Protein-Coupled; D054411:Receptors, Leptin; C431926:taste receptors, type 1; D052216:Glucagon-Like Peptide 1; D005905:Glyburide; D002118:Calcium
keywords: calcium imaging; gut; incretin; taste