title: Lactisole inhibits the glucose-sensing receptor T1R3 expressed in mouse pancreatic β-cells.
abstract: Glucose activates the glucose-sensing receptor T1R3 and facilitates its own metabolism in pancreatic β-cells. An inhibitor of this receptor would be helpful in elucidating the physiological function of the glucose-sensing receptor. The present study was conducted to examine whether or not lactisole can be used as an inhibitor of the glucose-sensing receptor. In MIN6 cells, in a dose-dependent manner, lactisole inhibited insulin secretion induced by sweeteners, acesulfame-K, sucralose and glycyrrhizin. The IC50 was ∼4 mmol/l. Lactisole attenuated the elevation of cytoplasmic Ca2+ concentration ([Ca2+]c) evoked by sucralose and acesulfame-K but did not affect the elevation of intracellular cAMP concentration ([cAMP]c) induced by these sweeteners. Lactisole also inhibited the action of glucose in MIN6 cells. Thus, lactisole significantly reduced elevations of intracellular [NADH] and intracellular [ATP] induced by glucose, and also inhibited glucose-induced insulin secretion. To further examine the effect of lactisole on T1R3, we prepared HEK293 cells stably expressing mouse T1R3. In these cells, sucralose elevated both [Ca2+]c and [cAMP]c. Lactisole attenuated the sucralose-induced increase in [Ca2+]c but did not affect the elevation of [cAMP]c. Finally, lactisole inhibited insulin secretion induced by a high concentration of glucose in mouse islets. These results indicate that the mouse glucose-sensing receptor was inhibited by lactisole. Lactisole may be useful in assessing the role of the glucose-sensing receptor in mouse pancreatic β-cells.
authors.affiliation: Institute for Molecular and Cellular RegulationGunma University, Maebashi 371-8512, JapanDepartment of General MedicineNational Defense Medical College, Tokorozawa, JapanSuntory Institute for Bioorganic ResearchOsaka, JapanDepartment of Internal MedicineShinshu University School of Medicine, Matsumoto, Japan Institute for Molecular and Cellular RegulationGunma University, Maebashi 371-8512, JapanDepartment of General MedicineNational Defense Medical College, Tokorozawa, JapanSuntory Institute for Bioorganic ResearchOsaka, JapanDepartment of Internal MedicineShinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Kunihisa
authors.initials: K
authors.lastname: Hamano
authors.affiliation: Institute for Molecular and Cellular RegulationGunma University, Maebashi 371-8512, JapanDepartment of General MedicineNational Defense Medical College, Tokorozawa, JapanSuntory Institute for Bioorganic ResearchOsaka, JapanDepartment of Internal MedicineShinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Institute for Molecular and Cellular RegulationGunma University, Maebashi 371-8512, JapanDepartment of General MedicineNational Defense Medical College, Tokorozawa, JapanSuntory Institute for Bioorganic ResearchOsaka, JapanDepartment of Internal MedicineShinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ohtsu
authors.affiliation: Institute for Molecular and Cellular RegulationGunma University, Maebashi 371-8512, JapanDepartment of General MedicineNational Defense Medical College, Tokorozawa, JapanSuntory Institute for Bioorganic ResearchOsaka, JapanDepartment of Internal MedicineShinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Longfei
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute for Molecular and Cellular RegulationGunma University, Maebashi 371-8512, JapanDepartment of General MedicineNational Defense Medical College, Tokorozawa, JapanSuntory Institute for Bioorganic ResearchOsaka, JapanDepartment of Internal MedicineShinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Johan
authors.initials: J
authors.lastname: Medina
authors.affiliation: Institute for Molecular and Cellular RegulationGunma University, Maebashi 371-8512, JapanDepartment of General MedicineNational Defense Medical College, Tokorozawa, JapanSuntory Institute for Bioorganic ResearchOsaka, JapanDepartment of Internal MedicineShinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Institute for Molecular and Cellular RegulationGunma University, Maebashi 371-8512, JapanDepartment of General MedicineNational Defense Medical College, Tokorozawa, JapanSuntory Institute for Bioorganic ResearchOsaka, JapanDepartment of Internal MedicineShinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Masuda
authors.affiliation: Institute for Molecular and Cellular RegulationGunma University, Maebashi 371-8512, JapanDepartment of General MedicineNational Defense Medical College, Tokorozawa, JapanSuntory Institute for Bioorganic ResearchOsaka, JapanDepartment of Internal MedicineShinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Mitsuhisa
authors.initials: M
authors.lastname: Komatsu
authors.affiliation: Institute for Molecular and Cellular RegulationGunma University, Maebashi 371-8512, JapanDepartment of General MedicineNational Defense Medical College, Tokorozawa, JapanSuntory Institute for Bioorganic ResearchOsaka, JapanDepartment of Internal MedicineShinshu University School of Medicine, Matsumoto, Japan ikojima@gunma-u.ac.jp.
authors.forename: Itaru
authors.initials: I
authors.lastname: Kojima
mesh_terms: D000818:Animals; D001555:Benzene Derivatives / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D019695:Glycyrrhizic Acid / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D013395:Sucrose / Q000031:analogs & derivatives / Q000494:pharmacology; D013549:Sweetening Agents / Q000494:pharmacology*; D013843:Thiazines / Q000494:pharmacology
chemical_list: D001555:Benzene Derivatives; D007328:Insulin; D043562:Receptors, G-Protein-Coupled; D013549:Sweetening Agents; D013843:Thiazines; C431926:taste receptors, type 1; D013395:Sucrose; D019695:Glycyrrhizic Acid; C026285:trichlorosucrose; D000242:Cyclic AMP; D005947:Glucose; C006362:acetosulfame; D002118:Calcium; C495512:lactisole
keywords: glucose; insulin secretion; sweet taste receptor; β-cell