%0 Journal Article %A Xudong Wang %A Qing Zhao %A Wang Xi %A Shangrong Zhang %A Jiwei Qin %A Jili Lv %A Yongzhe Che %A Weiyan Zuo %A Shu Jie Li %T Deficiency of Voltage-gated Proton Channel Hv1 Leads to hypoinsulinaemia, hyperglycemia and glucose intolerance in mice %D 2017 %R 10.1101/097816 %J bioRxiv %P 097816 %X 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. %U https://www.biorxiv.org/content/biorxiv/early/2017/01/03/097816.full.pdf