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

Biochem Biophys Res Commun. 2018 Jun 7;500(3):723-730. doi: 10.1016/j.bbrc.2018.04.143. Epub 2018 Apr 25.


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.

Keywords: Actin reorganization; Bitter taste receptors; Enteroendocrine L cell; Glucagon-like peptide-1; Live-cell imaging; Quinine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / drug effects
  • Actin Cytoskeleton / metabolism
  • Actins / metabolism*
  • Calcium / metabolism
  • Cell Line
  • Cyclic AMP / metabolism
  • Enteroendocrine Cells / drug effects
  • Enteroendocrine Cells / metabolism*
  • Exocytosis* / drug effects
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism
  • Glucagon-Like Peptide 1 / metabolism*
  • Humans
  • Intracellular Space / metabolism
  • KATP Channels / metabolism
  • Quinine / pharmacology*
  • Signal Transduction / drug effects
  • Taste*


  • Actins
  • KATP Channels
  • Glucagon-Like Peptide 1
  • Quinine
  • Cyclic AMP
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Calcium