Sucralose, an activator of the glucose-sensing receptor, increases ATP by calcium-dependent and -independent mechanisms

Endocrine Journal

Yoshiaki Ohtsu²  Longfei Li¹  Katsuyoshi Masuda³  Yuko Nakagawa¹  Itaru Kojima¹ 

[1] Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan;Department of Pediatrics, Graduate School of Medicine, Gunma University, Maebashi 371-8512, Japan;Suntory Global Innovation Center, Kyoto 619-0284, Japan

关键词: Sweet taste receptor;    Glucose metabolism;    β-cell;    Calcium;    ATP;   

DOI  :  10.1507/endocrj.EJ16-0217

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(27)Sucralose is an artificial sweetener and activates the glucose-sensing receptor expressed in pancreatic β-cells.Although sucralose does not enter β-cells nor acts as a substrate for glucokinase, it induces a marked elevation of intracellular ATP ([ATP]c).The present study was conducted to identify the signaling pathway responsible for the elevation of [ATP]c induced by sucralose.Previous studies have shown that sucralose elevates cyclic AMP (cAMP), activates phospholipase C (PLC) and stimulates Ca2+ entry by a Na+-dependent mechanism in MIN6 cells.The addition of forskolin induced a marked elevation of cAMP, whereas it did not affect [ATP]c.Carbachol, an activator of PLC, did not increase [ATP]c.In addition, activation of protein kinase C by dioctanoylglycerol did not affect [ATP]c.In contrast, nifedipine, an inhibitor of the voltage-dependent Ca2+ channel, significantly reduced [ATP]c response to sucralose.Removal of extracellular Na+ nearly completely blocked sucralose-induced elevation of [ATP]c.Stimulation of Na+ entry by adding a Na+ ionophore monensin elevated [ATP]c.The monensin-induced elevation of [ATP]c was only partially inhibited by nifedipine and loading of BAPTA, both of which completely abolished elevation of [Ca2+]c.These results suggest that Na+ entry is critical for the sucralose-induced elevation of [ATP]c.Both calcium-dependent and -independent mechanisms are involved in the action of sucralose.

【 授权许可】

Unknown