The signaling protein GIV/Girdin mediates the Nephrin-dependent insulin secretion of pancreatic islet β cells in response to high glucose

Wang, Hao; Yuan, Yingchao; Chang, Cong; Izumi, Tetsuro; Wang, Hong‐Hui; Yang, Jin‐Kui

doi:10.1016/j.jbc.2023.103045

Cited by 1 publication

(1 citation statement)

References 37 publications

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“…Human embryonic kidney (HEK) 293A cells (Cell Resource Center, Chinese Academy of Medical Sciences, Beijing, China) were cultured in high glucose DMEM containing 10% FBS and 1% penicillin–streptomycin. Pancreatic islets were isolated from mice through injection of 500 units/mL collagenase solution (type XI; Sigma) into the pancreatic duct, followed by mild shaking digestion at 37 °C for 20 min, and isolated islets were manually selected under a dissecting microscope, as described elsewhere [ 23 ]. Isolated islets were cultured overnight in RPMI 1640 medium containing 10% FBS and 1% penicillin–streptomycin.…”

Section: Methodsmentioning

confidence: 99%

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

Wang,

Li,

Yuan

et al. 2024

Cell. Mol. Life Sci.

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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.

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Section: Methodsmentioning

confidence: 99%