Sweet taste receptor signaling in beta cells mediates fructose-induced potentiation of glucose-stimulated insulin secretion
Sweet taste receptor signaling in beta cells mediates fructose-induced potentiation of glucose-stimulated insulin secretion
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DOI：
10.1073/pnas.1115183109
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发表时间：
2012-02-21
影响因子：
11.1
通讯作者：
Tyrberg, Bjoern
中科院分区：
文献类型：
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作者：
Kyriazis, George A.;Soundarapandian, Mangala M.;Tyrberg, Bjoern
餐后胰岛素释放受葡萄糖调节，但其他循环营养物质可能靶向β细胞并通过不同的信号传导途径增强葡萄糖刺激的胰岛素分泌。我们证明，果糖激活β细胞上的甜味受体（TRs），并与葡萄糖协同作用，以放大人类和小鼠胰岛中的胰岛素释放。甜味TR蛋白T1R2的遗传消融消除果糖诱导的胰岛素释放及其对体外和体内葡萄糖刺激的胰岛素分泌的增强作用。β细胞中的TR信号传导至少部分地与葡萄糖代谢途径平行触发，并导致细胞内钙的增加，这依赖于磷脂酶C（PLC）和瞬时受体电位阳离子通道，亚家族M，成员5（TRPM 5）的活化。我们的研究结果揭示了一个途径的调节胰岛素释放的餐后营养素，涉及β细胞甜TR信号。
Postprandial insulin release is regulated by glucose, but other circulating nutrients may target beta cells and potentiate glucose-stimulated insulin secretion via distinct signaling pathways. We demonstrate that fructose activates sweet taste receptors (TRs) on beta cells and synergizes with glucose to amplify insulin release in human and mouse islets. Genetic ablation of the sweet TR protein T1R2 obliterates fructose-induced insulin release and its potentiating effects on glucose-stimulated insulin secretion in vitro and in vivo. TR signaling in beta cells is triggered, at least in part, in parallel with the glucose metabolic pathway and leads to increases in intracellular calcium that are dependent on the activation of phospholipase C (PLC) and transient receptor potential cation channel, subfamily M, member 5 (TRPM5). Our results unveil a pathway for the regulation of insulin release by postprandial nutrients that involves beta cell sweet TR signaling.