Transient receptor potential cation channels in pancreatic β cells.

There is now overwhelming evidence that TRP channels might play a significant role in the regulation of insulin release from pancreatic β cells, which is until now insufficiently recognized. TRP channels are abundantly expressed on β cells. The focus of this review will be on cation channels from the melastatin TRP -subfamily. We will discuss how TRPM channels can influence Ca(2+) signaling in β cells. Knock out models of TRPM2 and TRPM5, which show a pre-diabetic phenotype, will be illustrative for this purpose. Based on these insights, TRPM5 will be critically evaluated as a potential drug target for diabetes type II therapy, which has received currently a high interest of the pharmaceutical industry. In addition, an unexpected role of the TRP channel TRPM3 as a gatekeeper of zinc, which is required for insulin storage, will be considered. Finally, we will critically discuss the use of mouse models for the unraveling of basic mechanisms of insulin release. The study of the role of TRP channels in the regulation of insulin release is of wide interest for fundamental research, evaluation of molecular mechanisms of disease and exploration of novel drug targets for metabolic diseases.