RT Journal Article SR Electronic T1 Deficiency of Voltage-gated Proton Channel Hv1 Leads to hypoinsulinaemia, hyperglycemia and glucose intolerance in mice JF bioRxiv FD Cold Spring Harbor Laboratory SP 097816 DO 10.1101/097816 A1 Xudong Wang A1 Qing Zhao A1 Wang Xi A1 Shangrong Zhang A1 Jiwei Qin A1 Jili Lv A1 Yongzhe Che A1 Weiyan Zuo A1 Shu Jie Li YR 2017 UL http://biorxiv.org/content/early/2017/01/03/097816.abstract AB Here, we demonstrate that the voltage-gated proton channel Hv1 represents a regulatory mechanism for insulin secretion of pancreatic islet β cell and glucose homeostasis. In vivo, Hv1-deficient mice display hypoinsulinaemia, hyperglycemia and glucose intolerance due to reduced insulin secretion, but normal peripheral insulin sensitivity. In vitro, islets from Hv1-deficient and heterozygous mice, β cells and islets with siRNA-mediated knockdown of Hv1 exhibit a marked defect in secretagogue-induced insulin secretion. A decrease in α and β cell masses has been observed in islets from Hv1-deficient mice. Furthermore, Hv1-deficient β cell has an impairment on glucose- and sulfonylurea-induced intracellular Ca2+ homeostasis and membrane depolarization. Collectively, our in vitro and in vivo results indicate that Hv1 is required for insulin secretion in the β cell and that dysfunction of Hv1 may contribute to the pathophysiology of type 2 diabetes. Our study sheds light on a new biological function of the proton channel.