title: Diverse signaling systems activated by the sweet taste receptor in human GLP-1-secreting cells.
abstract: Sweet taste receptor regulates GLP-1 secretion in enteroendocrine L-cells. We investigated the signaling system activated by this receptor using Hutu-80 cells. We stimulated them with sucralose, saccharin, acesulfame K and glycyrrhizin. These sweeteners stimulated GLP-1 secretion, which was attenuated by lactisole. All these sweeteners elevated cytoplasmic cyclic AMP ([cAMP]c) whereas only sucralose and saccharin induced a monophasic increase in cytoplasmic Ca(2+) ([Ca(2+)]c). Removal of extracellular calcium or sodium and addition of a Gq/11 inhibitor greatly reduced the [Ca(2+)]c responses to two sweeteners. In contrast, acesulfame K induced rapid and sustained reduction of [Ca(2+)]c. In addition, glycyrrhizin first reduced [Ca(2+)]c which was followed by an elevation of [Ca(2+)]c. Reductions of [Ca(2+)]c induced by acesulfame K and glycyrrhizin were attenuated by a calmodulin inhibitor or by knockdown of the plasma membrane calcium pump. These results indicate that various sweet molecules act as biased agonists and evoke strikingly different patterns of intracellular signals.
authors.affiliation: Institute for Molecular & Cellular Regulation, Gunma University, Maebashi 371-8512, Japan; Department of Pediatrics, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ohtsu
authors.affiliation: Institute for Molecular & Cellular Regulation, Gunma University, Maebashi 371-8512, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Institute for Molecular & Cellular Regulation, Gunma University, Maebashi 371-8512, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nagasawa
authors.affiliation: Gunma University Graduate School of Technology, Kiryu 376-8515, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Takeda
authors.affiliation: Department of Pediatrics, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Arakawa
authors.affiliation: Institute for Molecular & Cellular Regulation, Gunma University, Maebashi 371-8512, Japan. Electronic address: ikojima@gunma-u.ac.jp.
authors.forename: Itaru
authors.initials: I
authors.lastname: Kojima
mesh_terms: D001555:Benzene Derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism; D004386:Duodenum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D052216:Glucagon-Like Peptide 1 / Q000096:biosynthesis / Q000378:metabolism*; D019695:Glycyrrhizic Acid / Q000737:chemistry / Q000494:pharmacology; D020662:Guanine Nucleotide Exchange Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012439:Saccharin / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013395:Sucrose / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D013549:Sweetening Agents / Q000737:chemistry / Q000494:pharmacology*; D013843:Thiazines / Q000737:chemistry / Q000494:pharmacology
chemical_list: D001555:Benzene Derivatives; D002147:Calmodulin; D004791:Enzyme Inhibitors; D020662:Guanine Nucleotide Exchange Factors; C116122:RAPGEF3 protein, human; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D013549:Sweetening Agents; D013843:Thiazines; C431926:taste receptors, type 1; D013395:Sucrose; D019695:Glycyrrhizic Acid; D052216:Glucagon-Like Peptide 1; C026285:trichlorosucrose; D000242:Cyclic AMP; D053499:Plasma Membrane Calcium-Transporting ATPases; D012439:Saccharin; C006362:acetosulfame; D002118:Calcium; C495512:lactisole
keywords: Calcium; Cyclic AMP; GLP-1; Sweet taste receptor