KCNH6 channel promotes insulin exocytosis via interaction with Munc18-1 independent of electrophysiological processes.

Glucose-stimulated insulin secretion (GSIS) in pancreatic islet ß-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 ß-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 ß-cell-specific KCNH6 knockout (ßKO) exhibited impaired glucose tolerance and reduced insulin secretion, a phenomenon not explained by electrophysiological processes alone. Consistently, islets from KCNH6-ßKO 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.

[Pharmacokinetics of gypenoside XVâ ¡ in rats].

In this study, we established an HPLC-MS method to determine gypenoside XVⅡ in biosamples. The methodology results indicated that the linear range was 1-2 500 µg•L⁻¹ (r=0.996 3); intraday RSD values for high, medium and low concentrations were 9.9%, 3.0% 1.7%; interday RSD values were 16%, 14%, 2.5%; matrix effect ranged between 90.0%-100%, with RSD<15%. The recovery was more than 80.0%, with precision and accuracy in line with request. After the rats were orally and intravenously administered with gypenoside XVⅡ, the concentrations of gypenoside XVⅡ in plasma were determined, and pharmacokinetic parameter was calculated using pharmacokinetic software DAS 2.0. According to the main pharmacokinetic parameters of gypenoside XVⅡ, tmax was 0.17-0.20 h, t1/2 was 1.94-2.56 h, bioavailability of oral administration was 1.87%. The results indicated that the pharmacokinetic profiles of gypenoside XVⅡ were rapid absorption and distribution after oral administration, short time to peak and rapid elimination.