Pharmaceutical agents targeting KATP channel modulate sweet taste sensitivity in mice

Sweet detection involves at least two mechanisms: a G-protein coupled sweet taste receptor (Tas1r2/Tas1r3) and glucose transporters. As in pancreatic β-cells, glucose transport may lead to closure of ATP-sensitive potassium (K ATP ) channels. Since expression of K ATP channels in sweet taste cells has been reported, modulation of K ATP channel activity would affect sweet taste sensitivity. Here, we examined the effect of glibenclamide (a K ATP channel closer) and diazoxide (an opener) on mouse taste behavior. Glibenclamide selectively reduced taste sensitivity to glucose without affecting responses to sucrose or sucralose compared to insulin, suggesting selective impairment of the transporter-dependent pathway. In contrast, diazoxide broadly suppressed responses to all tested sweeteners, indicating a generalized effect on sweet detection. Neither drug altered responses to non-sweet taste. These findings suggest that pharmacological modulation of K ATP channel differently influences sweet taste; closers reduce glucose sensitivity whereas openers attenuate response to multiple sweeteners.