Reactive oxygen species (ROS) impairs pancreatic beta-cells and plays an important role in development of diabetes. Streptozotocin (STZ) can lead to beta-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 beta-cell damage. We found that deficiency of Hv1 obviously inhibits STZ-induced glucose intolerance in mice, and prevents the decrease in (3 cell mass and pancreatic insulin content from STZ-treatment. Further studies showed that loss of Hv1 significantly attenuates STZ-induced beta-cell damage and ROS production in pancreatic beta-cells. Our results suggest that Hv1 might contribute to development of diabetes through producing ROS. (C) 2018 Elsevier Inc. All rights reserved.