An alternative pathway for sweet sensation: possible mechanisms and physiological relevance
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INVITED REVIEW
An alternative pathway for sweet sensation: possible mechanisms and physiological relevance Elena von Molitor 1 & Katja Riedel 2 & Michael Krohn 2 & Rüdiger Rudolf 1,3 & Mathias Hafner 1 & Tiziana Cesetti 1 Received: 19 June 2020 / Revised: 14 September 2020 / Accepted: 23 September 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Sweet substances are detected by taste-bud cells upon binding to the sweet-taste receptor, a T1R2/T1R3 heterodimeric G proteincoupled 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 KATP 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. Keywords Taste-bud cells . Sweet-taste receptor . TAS1R2 . TAS1R3 . Artificial sweeteners . Cephalic-phase insulin release . Glucagon-like peptide-1 . Glucose transporters
Abbreviations CPIR Cephalic-phase insulin release DMNX Dorsal motor nucleus of vagus nerve GLP-1 Glucagon-like peptide-1 GLUT Glucose -transporter IP3 Inositol triphosphate KATP ATP-sensitive K+ channels NTS Nucleus of the solitary tract PLCβ2 Phospholipase-Cβ2 SGLT Sodium/glucose cotransporter T1R1 Taste receptor type 1 member 1
* Mathias Hafner [email protected] * Tiziana Cesetti [email protected] 1
Institute of Molecular and Cell Biology, Hochschule Mannheim, 68163 Mannheim, Germany
2
BRAIN AG, 64673 Zwingenberg, Germany
3
Interdisciplinary Center for Neurosciences, Heidelberg University, 69120 Heidelberg, Germany
T1R2 T1R3 TRPM5 VDCCs VRAC
Taste receptor type 1 member 2 Taste receptor type 1 member 3 Membrane-associated transient receptor potential channel subfamily M member 5 Voltage-dependent calcium channels Volume-regulated anion channel
Introduction Gustatory information is decoded by five primary taste modalities: sweet, bitter, umami, sour, and salty. Each is perceived by taste -bud cells [24, 43, 64, 155], which can be grouped into four types: type I has glia-like function, type II (receptor cell) detects umami, bitter, and
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