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

Abstract

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.