Effects of a bitter substance, denatonium benzoate, on pancreatic hormone secretion

There is increasing evidence linking bitter taste receptor (BTR) signalling to gut hormone secretion and glucose homeostasis. However, its effect on islet hormone secretion has been poorly characterised. This study investigated the effect of the bitter substance, denatonium benzoate (DB), on hormone secretion from mouse pancreatic islets and INS-1 832/13 cells. DB (0.5-1mM) augmented insulin secretion at both 2.8mM and 16.7mM glucose. This effect was no longer present at 5mM DB likely due to greater levels of cellular apoptosis. DB-stimulated insulin secretion involved closure of the K_ATP channel, activation of T2R signalling in beta-cells and intra-islet GLP-1 release. DB also enhanced glucagon and somatostatin secretion, but the underlying mechanism was less clear. Together, this study demonstrates that the bitter substance, DB, is a strong potentiator of islet hormone secretion independent of glucose. This observation highlights the potential for widespread off-target effects associated with the clinical use of bitter-tasting substances.