Figure 9. Schematic overview of intracellular pathways in type II taste receptor cells and pancreatic β-cells.

Important factors in the regulation of taste perception and insulin secretion, relevant for this work, are highlighted in this figure. The effects of stevioside through TRPM5 are highlighted with red arrows. In type II taste receptor cells, positive modulation of TRPM5 increases ATP release and afferent signalling from the receptor cell. In the pancreatic β-cell, upon glucose application β-cells display parallel V_m and [Ca²⁺]_cyt oscillations, which drive insulin secretion. TRPM5 is active during the lag phase in between bursts of action potentials, and determines the frequency of V_m and Ca²⁺ oscillations, which modulates insulin secretion: enhanced TRPM5 activity results in a higher oscillation frequency, which results in more insulin secretion. Note that steviol and its derivatives (for example, stevioside) only enhance TRPM5 activity and insulin secretion, but that glucose is the trigger for cell signalling. Instead, sulfonylureas such as glibenclamide (not depicted) block K_ATP channels directly and trigger Ca²⁺ signalling and insulin secretion independent of glucose transport.