Voltage-Gated Na~+ Channels Of INS-1 Cells Is Involved In Regulating Extracellular Glucose Levels

Background/Aims:Islet beta cells??-cells?are unique cells that play a critical role in glucose homeostasis by secreting insulin in response to increased glucose levels.Voltage-gated ion channels in?-cells,such as K⁺and Ca²⁺channels,contribute to insulin secretion.The response of voltage-gated Na⁺channel?VGSC/Na_V?in?-cells to the changes in glucose levels remains unknown.This work aims to determine the role of extracellular glucose on the regulation of VGSC.Methods:The effect of glucose on VGSC currents(I_Na)was investigated in insulin-secreting?-cell line?INS-1?cells of rats using whole-cell patch clamp techniques,and the effects of glucose on insulin content and cell viability were determined using Enzyme-Linked Immunosorbent Assay?ELISA?and Methylthiazolyldiphenyl-tetrazolium Bromide?MTT?assay methods respectively.Results:Our results show that extracellular glucose application can inhibit the peak of I_Na in a concentration-dependent manner.Glucose concentration of 18 mM reduced the amplitude of I_Na,suppressed the I_Na of steady-state activation,shifted the steady-state inactivation curves of I_Na to negative potentials,and prolonged the time course of I_Na recovery from inactivation.Glucose also enhanced the activity-dependent attenuation of I_Na and reduced the fraction of activated channels.Furthermore,18 mM glucose or low concentration?0.1?M and0.2?M?of tetrodotoxin?TTX,a VGSC-specific blocker?partially inhibited the activity of VGSC and also improved insulin synthesis.Conclusion:These results revealed that extracellular glucose application enhances the insulin synthesis in INS-1cells and the mechanism through the partial inhibition on I_Na channel is involved.Our results innovatively suggest that VGSC plays a vital role in modulating glucose homeostasis.