Glucose elicits cephalic-phase insulin release in mice by activating KATP channels in taste cells
Glucose elicits cephalic-phase insulin release in mice by activating KATP channels in taste cells
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DOI：
10.1152/ajpregu.00433.2016
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发表时间：
2017-04-01
影响因子：
2.8
通讯作者：
Sclafani, Anthony
中科院分区：
文献类型：
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作者：
Glendinning, John I.;Frim, Yonina G.;Sclafani, Anthony
糖的味道会引起头相胰岛素释放（CPIR），从而限制与膳食相关的血糖升高。然而，人们对触发 CPIR 的味觉机制知之甚少。我们询问以下任何味觉刺激物的口腔刺激是否会引起小鼠的 CPIR：葡萄糖、蔗糖、麦芽糖、果糖、多糖、糖精、三氯蔗糖、AceK、SC45647 或不可代谢的糖类似物。唯一引起 CPIR 的味觉刺激是葡萄糖和含葡萄糖的糖类（蔗糖、麦芽糖、多糖）。当我们将 α-葡萄糖苷酶抑制剂（阿卡波糖）与后三种糖混合时，小鼠不再表现出 CPIR。这表明碳水化合物在口腔中水解，释放的葡萄糖触发了 CPIR。我们还发现，增加口服葡萄糖刺激的强度或持续时间会导致 CPIR 幅度相应增加。为了确定葡萄糖特异性味觉信号通路的组成部分，我们检查了 Calhm1、P2X2 + P2X3、SGLT1 和 Sur1 的必要性。在这些蛋白质中，只有 Sur1 是 CPIR 所必需的。然而，Sur1 对于味觉介导的糖类吸引力来说并不是必需的。鉴于 Sur1 是 ATP 敏感 K+ 通道 (K-ATP) 通道的一个亚基，并且该通道作为胰腺 β 细胞中葡萄糖感应途径的一部分，我们询问 K-ATP 通道是否在味觉细胞中发挥类似的作用。我们发现，用已知可增加（格列本脲）或减少（二氮嗪）K-ATP 信号传导的药物进行口服刺激，会导致葡萄糖刺激的 CPIR 产生相应的变化。我们认为 K-ATP 通道是味觉细胞中介导葡萄糖诱导的 CPIR 的新型信号传导途径的一部分。
The taste of sugar elicits cephalic-phase insulin release (CPIR), which limits the rise in blood glucose associated with meals. Little is known, however, about the gustatory mechanisms that trigger CPIR. We asked whether oral stimulation with any of the following taste stimuli elicited CPIR in mice: glucose, sucrose, maltose, fructose, Polycose, saccharin, sucralose, AceK, SC45647, or a nonmetabolizable sugar analog. The only taste stimuli that elicited CPIR were glucose and the glucose-containing saccharides (sucrose, maltose, Polycose). When we mixed an alpha-glucosidase inhibitor (acarbose) with the latter three saccharides, the mice no longer exhibited CPIR. This revealed that the carbohydrates were hydrolyzed in the mouth, and that the liberated glucose triggered CPIR. We also found that increasing the intensity or duration of oral glucose stimulation caused a corresponding increase in CPIR magnitude. To identify the components of the glucose-specific taste-signaling pathway, we examined the necessity of Calhm1, P2X2 + P2X3, SGLT1, and Sur1. Among these proteins, only Sur1 was necessary for CPIR. Sur1 was not necessary, however, for taste-mediated attraction to sugars. Given that Sur1 is a subunit of the ATP-sensitive K+ channel (K-ATP) channel and that this channel functions as a part of a glucose-sensing pathway in pancreatic beta-cells, we asked whether the K-ATP channel serves an analogous role in taste cells. We discovered that oral stimulation with drugs known to increase (glyburide) or decrease (diazoxide) K-ATP signaling produced corresponding changes in glucose-stimulated CPIR. We propose that the K-ATP channel is part of a novel signaling pathway in taste cells that mediates glucose-induced CPIR.