Label="BACKGROUND/AIMS" NlmCategory="OBJECTIVE">The release of insulin in response to increased levels of glucose in the blood strongly depends on Ca<sup>2+</sup> influx into pancreatic beta cells by the opening of voltage-gated Ca<sup>2+</sup> channels. Transient Receptor Potential Melastatin 3 proteins build Ca<sup>2+</sup> permeable, non-selective cation channels serving as pain sensors of noxious heat in the peripheral nervous system. TRPM3 channels are also strongly expressed in pancreatic beta cells that respond to the TRPM3 agonist pregnenolone sulfate with Ca<sup>2+</sup> influx and increased insulin release. Therefore, we hypothesized that in beta cells TRPM3 channels may contribute to pregnenolone sulfate- as well as to glucose-induced insulin release.