HV-1

High glucose (HG)-induced oxidative stress contributes to the dysfunction of pancreatic β cells in diabetes. The voltage-gated proton channel Hv1 has been proposed to support reactive oxygen species (ROS) production during respiratory bursts. However, the effect of Hv1 on glucotoxicity in pancreatic β cells is not clear yet. In this study, we examined the protective effects of Hv1-deficiency in HG cultured β cells. Following 48 h of treatment with 30 mM high glucose, Hv1 KO β cells showed higher cell viability, lower cell apoptosis and a more stable insulin gene expression level compared to WT β cells. In both control and HG cultured β cells, deficiency of Hv1 decreased the glucose- and PMA-induced ROS production. Finally, HG incubation led to NOX4 upregulation in WT β cells, which could be inhibited by HV1 deficiency. In conclusion, Hv1-deficiency prevents the HG treatment-induced NOX4 upregulation and protects β cells from glucotoxicity.

Reactive oxygen species (ROS) impairs pancreatic β-cells and plays an important role in development of diabetes. Streptozotocin (STZ) can lead to β-cell dysfunction via inducing ROS production. The voltage-gated proton channel Hv1 contributes a majority of the charge compensation required for ROS production. Here, we investigated the effects of Hv1 on STZ-induced β-cell damage. We found that deficiency of Hv1 obviously inhibits STZ-induced glucose intolerance in mice, and prevents the decrease in β-cell mass and pancreatic insulin content from STZ-treatment. Further studies showed that loss of Hv1 significantly attenuates STZ-induced β-cell damage and ROS production in pancreatic β-cells. Our results suggest that Hv1 might contribute to development of diabetes through producing ROS.