The Transient Receptor Potential family of ion channels is a collection of 27 genes, all constituting cation channel proteins. There is now overwhelming evidence that TRP channels might play a significant role in the regulation of insulin release from pancreatic b cells. TRP channels are abundantly expressed on b cells. The focus of this talk will be on cation channels from the melastatin TRP subfamily. We will discuss how TRPM channels can influence Ca²⁺ signaling in b cells. Knock out models of TRPM2 and TRPM5, which show a pre-diabetic phenotype will be discussed. Especially our recent data on the role of TRPM5 in glucose stimulated islets pancreatic will be illustrative for the potential role of TRP channels as drug targets for diabetes type II therapy. In addition, an unexpected role of the TRP channel TRPM3 as a gatekeeper of zinc, which is required for insulin storage, will be considered. 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.