TRPM5 is a target in the modulation of taste perception and insulin secretion (133.4)

Abstract

TRPM5 is a monovalent cation selective ion channels, activated by an increase of the intracellular Ca2+ concentration. Physiologically, TRPM5 is a key player in the transduction of taste signals and plays a role in the release of insulin from pancreatic ß‐cells. To date no pharmacological tools are available to evaluate the potential of TRPM5 as drug target for taste modulation or as insulin secretagogue. Here we show that the TRPM5 ion channel has potential as a target to stimulate insulin secretion in a mouse model We present a new class of compounds capable of potentiating TRPM5 signaling and analyze their working mechanism. We show activation of TRPM5 in a heterologous overexpression system and in a murine animal model. We show potentiation of sweet and bitter taste in a TRPM5 dependent way, using a two bottle preference test. Furthermore we observe increased glucose induced activity in the insulin secreting islets of Langerhans upon perfusion with our activator. These effects were completely abolished in TRPM5 knock‐out mice. In the high fat fed mouse, a model for type II diabetes, we showed that activating TRPM5 with our compound allows them to maintain a healthier glucose metabolism and delays the development of diabetes.