Diverse signaling systems activated by the sweet taste receptor in human GLP-1-secreting cells

作者：Ohtsu Yoshiaki; Nakagawa Yuko; Nagasawa Masahiro; Takeda Shigeki; Arakawa Hirokazu; Kojima Itaru^*

来源：Molecular and Cellular Endocrinology, 2014, 394(1-2): 70-79.

DOI：10.1016/j.mce.2014.07.004

• Calcium
• Cyclic AMP
• Sweet taste receptor
• GLP-1

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 Ca2+ ([Ca2+](c)). Removal of extracellular calcium or sodium and addition of a G(q/11) inhibitor greatly reduced the [Ca2+](c) responses to two sweeteners. In contrast, acesulfame K induced rapid and sustained reduction of [Ca2+](c). In addition, glycyrrhizin first reduced [Ca2+](c) which was followed by an elevation of [Ca2+](c). Reductions of [Ca2+](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.

• 出版日期2014-8-25