TY - JOUR T1 - Deficiency of Voltage-gated Proton Channel Hv1 Leads to hypoinsulinaemia, hyperglycemia and glucose intolerance in mice JF - bioRxiv DO - 10.1101/097816 SP - 097816 AU - Xudong Wang AU - Qing Zhao AU - Wang Xi AU - Shangrong Zhang AU - Jiwei Qin AU - Jili Lv AU - Yongzhe Che AU - Weiyan Zuo AU - Shu Jie Li Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/01/03/097816.abstract N2 - 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. ER -