Sweet substances are detected by taste-bud cells upon binding to the sweet-taste receptor, a T1R2/T1R3 heterodimeric G protein-coupled receptor. In addition, experiments with mouse models lacking the sweet-taste receptor or its downstream signaling components led to the proposal of a parallel “alternative pathway” that may serve as metabolic sensor and energy regulator. Indeed, these mice showed residual nerve responses and behavioral attraction to sugars and oligosaccharides but not to artificial sweeteners. In analogy to pancreatic β cells, such alternative mechanism, to sense glucose in sweet-sensitive taste cells, might involve glucose transporters and K_ATP channels. Their activation may induce depolarization-dependent Ca²⁺ signals and release of GLP-1, which binds to its receptors on intragemmal nerve fibers. Via unknown neuronal and/or endocrine mechanisms, this pathway may contribute to both, behavioral attraction and/or induction of cephalic-phase insulin release upon oral sweet stimulation. Here, we critically review the evidence for a parallel sweet-sensitive pathway, involved signaling mechanisms, neural processing, interactions with endocrine hormonal mechanisms, and its sensitivity to different stimuli. Finally, we propose its physiological role in detecting the energy content of food and preparing for digestion.

甜味物质在与甜味受体（一种 T1R2/T1R3 异二聚体 G 蛋白偶联受体）结合后被味蕾细胞检测到。此外，对缺乏甜味受体或其下游信号成分的小鼠模型进行的实验导致提出了一种平行的“替代途径”，可以作为代谢传感器和能量调节器。事实上，这些小鼠对糖和寡糖表现出残留的神经反应和行为吸引力，但对人造甜味剂则没有。与胰腺 β 细胞类似，这种在甜味敏感味觉细胞中感知葡萄糖的替代机制可能涉及葡萄糖转运蛋白和 K _ATP通道。它们的激活可能会诱导去极化依赖性 Ca ²⁺信号和 GLP-1 的释放，GLP-1 与其在牙龈内神经纤维上的受体结合。通过未知的神经元和/或内分泌机制，该途径可能有助于行为吸引和/或在口服甜味刺激时诱导头期胰岛素释放。在这里，我们批判性地审查了平行甜味敏感途径的证据，涉及信号机制、神经处理、与内分泌激素机制的相互作用及其对不同刺激的敏感性。最后，我们提出了它在检测食物的能量含量和准备消化方面的生理作用。