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. 2018 Aug 4;16:76–87. doi: 10.1016/j.molmet.2018.07.013

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© 2018 The Authors

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

PMC Copyright notice

KDT501 signals through the bitter taste receptor mTas2r108. (A) Secretion of active GLP-1 into media from STC-1 cells exposed to the indicated compounds for 1 h. Forskolin (20 μM)/IBMX (100 μM) cocktail serves as positive control (n = 3). Representative intracellular calcium traces (n = 3) induced by KDT501 in HEK293 cells stably-expressing a Gα15-gustducin chimera and transiently transfected with (B) mouse Tas2r108 or (C) human TAS2R1. Calcium traces are shown after mock subtraction; RFU = relative fluorescence units. (D) Intracellular calcium mobilization response to KDT501 (10 μM) in STC-1 cells stably-expressing scramble shRNA or shRNA targeting Tas2r108. The response to KDT501 is abolished in cells depleted of Tas2r108 (n = 6). (E) Secretion of active GLP-1 in Tas2r108 knockdown STC-1 cells. Data presented as means ± SD in A and E, and means ± SEM in D. Statistical significance was calculated using Student's t test in A, and two-way ANOVA in E. *p < 0.05, ***p < 0.005 relative to vehicle-treated or Tas2r108 knockdown cells.