Bitter tastant quinine modulates glucagon-like peptide-1 exocytosis from clonal GLUTag enteroendocrine L cells via actin reorganization

• Published in: Biochemical and biophysical research communications Vol. 500; no. 3; pp. 723 - 730
• Main Authors: Harada, Kazuki, Sakaguchi, Hidekazu, Sada, Shoko, Ishida, Rika, Hayasaka, Yuki, Tsuboi, Takashi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.06.2018
• Subjects: 60 APPLIED LIFE SCIENCES; Actin reorganization; Bitter taste receptors; ENDOPLASMIC RETICULUM; Enteroendocrine L cell; GASTROINTESTINAL TRACT; GLUCAGON; Glucagon-like peptide-1; GLUCOSE; Live-cell imaging; MESSENGER-RNA; MICE; QUININE; RECEPTORS; GLP-1; PLC; PKA; Live-cell imaging; Tas2R; Epac; Quinine; Glucagon-like peptide-1; KATP channels; Enteroendocrine L cell; Actin reorganization; Bitter taste receptors; TRPM5; Fsk
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2018.04.143

Enteroendocrine L cells in the gastrointestinal tract secrete glucagon-like peptide-1 (GLP-1), which plays an important role in glucose homeostasis. Here we investigated the effect of bitter tastant quinine on GLP-1 secretion using clonal GLUTag mouse enteroendocrine L cells. We found that GLUTag cells expressed putative quinine receptors at mRNA levels. Although application of quinine resulted in an increase of intracellular Ca2+ levels, which was mediated by Ca2+ release from the endoplasmic reticulum and Ca2+ influx through voltage-sensitive Ca2+ channels, quinine had little effect on GLP-1 secretion. Total internal reflection fluorescence microscopy and immunocytochemistry revealed that GLP-1-containing vesicles remained unfused with the plasma membrane and facilitated actin polymerization beneath the plasma membrane after application of quinine, respectively. Interestingly, application of forskolin together with quinine induced GLP-1 exocytosis from the cells. These results suggest that quinine does not induce GLP-1 secretion because it facilitates Ca2+ increase and actin reorganization but not cAMP increase, and both Ca2+ and cAMP are essential for GLP-1 secretion. •Various bitter taste receptors were expressed in GLUTag cells.•Quinine increased the intracellular Ca2+ levels but did not promote GLP-1 secretion.•Quinine caused actin reorganization and suppressed exocytosis of GLP-1 vesicles.•Application of forskolin in quinine-treated GLUTag cells enhanced GLP-1 exocytosis.