Deficiency of Voltage-gated Proton Channel Hv1 Leads to hypoinsulinaemia, hyperglycemia and glucose intolerance in mice

Wang, X.; Zhao, Q.; Xi, W.; Zhang, S.; Qin, J.; Lv, J.; Che, Y.; Zuo, W.; Li, S. J.

doi:10.1101/097816

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bioRxiv · 10.1101/097816

Deficiency of Voltage-gated Proton Channel Hv1 Leads to hypoinsulinaemia, hyperglycemia and glucose intolerance in mice

Wang, X.·Zhao, Q.·Xi, W.·Zhang, S.·Qin, J.·Lv, J.·Che, Y.·Zuo, W.·Li, S. J.

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Abstract

Here, we demonstrate that the voltage-gated proton channel Hv1 represents a regulatory mechanism for insulin secretion of pancreatic islet {beta} cell. In vivo, Hv1-de[fi]cient mice display hyperglycemia and glucose intolerance due to reduced insulin secretion, but normal peripheral insulin sensitivity. In vitro, islets of Hv1-de[fi]cient and heterozygous mice, INS-1 (832/13) cells with siRNA-mediated knockdown of Hv1 exhibit a marked defect in glucose- and K+-induced insulin secretion. Hv1 de[fi]ciency decreases both insulin and proinsulin contents, and limits glucose-induced Ca2+ entry and membrane depolarization. Furthermore, loss of Hv1 increases insulin-containing granular pH and decreases cytosolic pH. In addition, histologic studies show a decrease in {beta} cell mass in islets of Hv1-deficient mice. Collectively, our results indicate that Hv1 supports insulin secretion in the {beta} cell by calcium entry, membrane depolarization and intracellular pH regulation.

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Wang, X., Zhao, Q., Xi, W., Zhang, S., Qin, J., Lv, J., Che, Y., Zuo, W., Li, S. J.. 2017-01-03. Deficiency of Voltage-gated Proton Channel Hv1 Leads to hypoinsulinaemia, hyperglycemia and glucose intolerance in mice. https://doi.org/10.1101/097816

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