2. Academic Validation
  3. Lactisole inhibits the glucose-sensing receptor T1R3 expressed in mouse pancreatic β-cells

Lactisole inhibits the glucose-sensing receptor T1R3 expressed in mouse pancreatic β-cells

  • J Endocrinol. 2015 Jul;226(1):57-66. doi: 10.1530/JOE-15-0102.
Kunihisa Hamano 1,  Yuko Nakagawa 2,  Yoshiaki Ohtsu 2,  Longfei Li 2,  Johan Medina 2,  Yuji Tanaka 2,  Katsuyoshi Masuda 2,  Mitsuhisa Komatsu 2,  Itaru Kojima 3
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 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.
PMID: 25994004 DOI: 10.1530/JOE-15-0102
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.

Keywords

glucose; insulin secretion; sweet taste receptor; β-cell.

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