Sugar-induced cephalic-phase insulin release is mediated by a T1r2+T1r3-independent taste transduction pathway in mice
Sugar-induced cephalic-phase insulin release is mediated by a T1r2+T1r3-independent taste transduction pathway in mice
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DOI：
10.1152/ajpregu.00056.2015
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发表时间：
2015-09-15
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.;Stano, Sarah;Sclafani, Anthony
食物的感官刺激会引起头相反应，从而促进消化和营养吸收。其中一种反应是头相胰岛素释放 (CPIR)，可增强葡萄糖耐量。关于激活 CPIR 的化学感应机制知之甚少。我们在 C57BL/6 (B6) 和 T1r3 敲除 (KO) 小鼠中研究了甜味受体 (T1r2+T1r3) 对糖诱导的 CPIR 的贡献。首先，我们测量了口服（即正常摄入）或胃内 (IG) 2.8 M 葡萄糖后的胰岛素释放和葡萄糖耐量。两组小鼠在口服但未注射 IG 后均表现出 CPIR，并且该 CPIR 改善了葡萄糖耐量。其次，我们检查了 CPIR 的特异性。两组小鼠在口服 1 M 葡萄糖和 1 M 蔗糖后均表现出 CPIR，但仅口服 1 M 果糖或水后则没有表现出 CPIR。第三，我们在短期可接受性测试中研究了对相同三种糖溶液的行为吸引力。 B6 小鼠对糖溶液的舔舐程度高于对水的舔舐程度，而 T1r3 KO 小鼠对糖溶液的舔舐程度并不比对水的舔舐程度高。最后，我们检查了鼓索 (CT) 神经对每种糖的反应。两组小鼠均表现出对糖的 CT 神经反应，但 B6 小鼠的反应更强。我们认为小鼠拥有两种糖味传导途径。一种介导对糖的行为吸引力，需要完整的 T1r2+T1r3。另一个介导 CPIR，但不需要完整的 T1r2+T1r3。如果后一种味觉传导途径存在于人类中，那么它应该为开发控制血糖的新疗法提供机会。
Sensory stimulation from foods elicits cephalic phase responses, which facilitate digestion and nutrient assimilation. One such response, cephalic-phase insulin release (CPIR), enhances glucose tolerance. Little is known about the chemosensory mechanisms that activate CPIR. We studied the contribution of the sweet taste receptor (T1r2+T1r3) to sugar-induced CPIR in C57BL/6 (B6) and T1r3 knockout (KO) mice. First, we measured insulin release and glucose tolerance following oral (i.e., normal ingestion) or intragastric (IG) administration of 2.8 M glucose. Both groups of mice exhibited a CPIR following oral but not IG administration, and this CPIR improved glucose tolerance. Second, we examined the specificity of CPIR. Both mouse groups exhibited a CPIR following oral administration of 1 M glucose and 1 M sucrose but not 1 M fructose or water alone. Third, we studied behavioral attraction to the same three sugar solutions in short-term acceptability tests. B6 mice licked more avidly for the sugar solutions than for water, whereas T1r3 KO mice licked no more for the sugar solutions than for water. Finally, we examined chorda tympani (CT) nerve responses to each of the sugars. Both mouse groups exhibited CT nerve responses to the sugars, although those of B6 mice were stronger. We propose that mice possess two taste transduction pathways for sugars. One mediates behavioral attraction to sugars and requires an intact T1r2+T1r3. The other mediates CPIR but does not require an intact T1r2+T1r3. If the latter taste transduction pathway exists in humans, it should provide opportunities for the development of new treatments for controlling blood sugar.