{Reference Type}: Journal Article
{Title}: KCNH6 channel promotes insulin exocytosis via interaction with Munc18-1 independent of electrophysiological processes.
{Author}: Wang H;Li Q;Yuan YC;Han XC;Cao YT;Yang JK;
{Journal}: Cell Mol Life Sci
{Volume}: 81
{Issue}: 1
{Year}: 2024 Feb 13
{Factor}: 9.207
{DOI}: 10.1007/s00018-024-05134-1
{Abstract}: Glucose-stimulated insulin secretion (GSIS) in pancreatic islet β-cells primarily relies on electrophysiological processes. Previous research highlighted the regulatory role of KCNH6, a member of the Kv channel family, in governing GSIS through its influence on β-cell electrophysiology. In this study, we unveil a novel facet of KCNH6's function concerning insulin granule exocytosis, independent of its conventional electrical role. Young mice with β-cell-specific KCNH6 knockout (βKO) exhibited impaired glucose tolerance and reduced insulin secretion, a phenomenon not explained by electrophysiological processes alone. Consistently, islets from KCNH6-βKO mice exhibited reduced insulin secretion, conversely, the overexpression of KCNH6 in murine pancreatic islets significantly enhanced insulin release. Moreover, insulin granules lacking KCNH6 demonstrated compromised docking capabilities and a reduced fusion response upon glucose stimulation. Crucially, our investigation unveiled a significant interaction between KCNH6 and the SNARE protein regulator, Munc18-1, a key mediator of insulin granule exocytosis. These findings underscore the critical role of KCNH6 in the regulation of insulin secretion through its interaction with Munc18-1, providing a promising and novel avenue for enhancing our understanding of the Kv channel in diabetes mechanisms.