TY  - GEN
A1  - Molitor, Elena von
KW  - taste
KW  -  spheroid
KW  -  perfusion
KW  -  live calcium imaging
KW  -  GLP-1
KW  -  CPIR
KW  -  light sheet fluorescence microscopy
N2  - Canonically, sweet perception is mediated by specific T1R2/T1R3 sweet taste G-protein coupled receptors expressed in taste cells of the tongue. However, mice lacking these receptors or their downstream signaling components are still able to recognize natural sugars. Conversely, they do not perceive artificial sweeteners, which are mostly canonical sweet taste receptor agonists, suggesting the existence of a parallel ?alternative pathway? for sweet perception. To address the molecular pathways, complexity and physiological relevance of sweet taste sensation, this study combines a deep literature survey on sweet taste biology with experimental work using 3D cell cultures of immortalized human tongue cells (HTC-8). 
The literature research revealed that sweet-sensitive taste cells may take up monosaccharides via Glucose transporters (GLUT/SGLT1) to induce depolarization-dependent Ca2+ signals upon oxidative metabolism and KATP channel inactivation. Disaccharides can activate this signal path upon digestion from taste cell-expressed Brush Boarder enzymes. Alternatively, disaccharides may be taken up with elusive transporters, induce osmotic swelling and activate volume regulated anion channels. Via unidentified neuronal and/or endocrine mechanisms, sweet taste receptor-independent pathways may contribute to behavioral attraction but may also induce cephalic phase Insulin release upon GLP 1 secretion from taste cells. This would suggest that the alternative pathway may prepare the body for digestion, while the canonical pathway might be rather responsible for the hedonic value of sugars. Since taste differs among species and human samples are limited, most hypotheses of the alternative pathway remain rather vague and are often based on cells of other organs that express extraoral sweet taste receptors and canonical downstream molecules like gastro-intestinal or pancreatic cells.
 
Since perfused live imaging experiments conducted in this study revealed that individual HTC 8 cells responded to KCl, sweet and bitter stimulation, they might belong to the newly described broadly-sensitive taste cells, which is in contrast with the assumption that diverse taste modalities use different signaling pathways in distinct cell types. A preliminary transcriptome analysis of HTC 8 spheroids corroborated the finding that taste is not exclusively transduced by the canonical pathway. Accordingly, bitter responses of HTC-8 spheroids might have been mediated by family members of the canonical signaling pathway, while sugars may have used the alternative pathway, since spheroids were not sensitive to the artificial sweetener Acesulfame K and related signal molecules of the alternative signal pathway were expressed upon 3D culture of HTC-8 cells. Although the here established model contains several limitations and needs further adjustment it might serve as a first testing platform to obtain human-derived data on taste physiology in a higher throughput than in human subjects. Thereby, it may support the search for new sugar alternatives and to combat the current sugar overconsumption which goes along with a sickening society.
TI  - Human tongue-cell derived spheroids suggest 
that multiple pathways and molecules are involved in 
the sweet gustatory sense
AV  - public
Y1  - 2021///
ID  - heidok30052
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/30052/
CY  - Heidelberg
ER  -