Analysis on the mechanism of enhancing insulin secretion by TRPM2 channel in a pancreatic β-cell

Abstract

It has been reported that the activation of the Ca²⁺-permeable transient receptor potential melastatin2 (TRPM2) channel enhances a pancreatic β-cell's insulin secretion. Further, it increases the resting potential, and prolongs the burst duration of the pancreatic β-cell. However, the mechanism by which the TRPM2 channel activation enhances insulin secretion is unknown. Therefore, in this paper, using a mathematical model that represents the dynamics of the membrane potential, we investigate the reproducibility of the results obtained from physiological experiments, and reveal the mechanism of enhancing insulin secretion. We demonstrate that the TRPM2 channel activation prolongs the burst duration when the TRPM2 reversal potential is close to the value observed in the physiological experiments. This could be a plausible theoretical explanation of the experimental value of the TRPM2 reversal potential. In addition, we reveal that the TRPM2 channel activates the voltage-dependent and Ca²⁺-sensitive channels with large conductance, thereby inducing insulin secretion.