Sweet taste receptor expressed in pancreatic β-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion

Background: Sweet taste receptor is expressed in the taste buds and enteroendocrine cells acting as a sugar sensor. We investigated the expression and function of the sweet taste receptor in MIN6 cells and mouse islets. Methodology/Principal Findings: The expression of the sweet taste receptor was determined by RT-PCR and immunohistochemistry. Changes in cytoplasmic Ca²⁺ ([Ca²⁺]_c) and cAMP ([cAMP]_c) were monitored in MIN6 cells using fura-2 and Epac1-camps. Activation of protein kinase C was monitored by measuring translocation of MARCKS-GFP. Insulin was measured by radioimmunoassay. mRNA for T1R2, T1R3, and gustducin was expressed in MIN6 cells. In these cells, artificial sweeteners such as sucralose, succharin, and acesulfame-K increased insulin secretion and augmented secretion induced by glucose. Sucralose increased biphasic increase in [Ca²⁺]_c. The second sustained phase was blocked by removal of extracellular calcium and addition of nifedipine. An inhibitor of inositol(1, 4, 5)-trisphophate receptor, 2-aminoethoxydiphenyl borate, blocked both phases of [Ca²⁺]_c response. The effect of sucralose on [Ca²⁺]_c was inhibited by gurmarin, an inhibitor of the sweet taste receptor, but not affected by a G_q inhibitor. Sucralose also induced sustained elevation of [cAMP]_c, which was only partially inhibited by removal of extracellular calcium and nifedipine. Finally, mouse islets expressed T1R2 and T1R3, and artificial sweeteners stimulated insulin secretion. Conclusions: Sweet taste receptor is expressed in β-cells, and activation of this receptor induces insulin secretion by Ca²⁺ and cAMP-dependent mechanisms.