Hamano K, Nakagawa Y, Ohtsu Y, Li L, Medina J (IMCR, Gunma Univ.) Tanaka Y (National Defense Medical College) Masuda K (Suntory Institute) Komatsu M (Shinshu Univ. School of Medicine) Kojima I (IMCR, Gunma Univ.)
About
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 approximately 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.
Paper information
Lactisol inhibits the glucose-sensing receptor T1R3 expressed in mouse pancreatic β-cells.
Hamano K, Nakagawa Y, Ohtsu Y, Li L, Medina J, Tanaka Y, Masuda K, Komatsu M, Kojima I.
J Endocrinol JOE-15-0102. [Epub ahead of print]
Online URL
http://www.ncbi.nlm.nih.gov/pubmed/25994004
