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  • From Hyper- to Hypoinsulinemia and Diabetes: Effect of KCNH6 on Insulin Secretion

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    Author(s)
    Yang, Jin-Kui
    Lu, Jing
    Yuan, Sha-Sha
    Asan
    Cao, Xi
    Qiu, Hai-Yan
    Shi, Ting-Ting
    Yang, Fang-Yuan
    Li, Qian
    Liu, Cui-Ping
    Wu, Qian
    Wang, Yu-Hui
    Huang, Hai-Xia
    Kayoumu, Abudurexiti
    Feng, Jian-Ping
    Xie, Rong-Rong
    Zhu, Xiao-Rong
    Liu, Chang
    Yang, Guang-Ran
    Zhang, Ming-Rong
    Xie, Chun-Lan
    Chen, Chen
    Zhang, Bo
    Liu, George
    Zhang, Xiu-Qing
    Xu, Aimin
    Griffith University Author(s)
    Chen, Chen
    Year published
    2018
    Metadata
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    Abstract
    Glucose-stimulated insulin secretion from islet β cells is mediated by K ATP channels. However, the role of non-K ATP K + channels in insulin secretion is largely unknown. Here, we show that a non-K ATP K + channel, KCNH6, plays a key role in insulin secretion and glucose hemostasis in humans and mice. KCNH6 p.P235L heterozygous mutation co-separated with diabetes in a four-generation pedigree. Kcnh6 knockout (KO) or Kcnh6 p.P235L knockin (KI) mice had a phenotype characterized by changing from hypoglycemia with hyperinsulinemia to hyperglycemia with insulin deficiency. Islets from the young KO mice had increased intracellular ...
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    Glucose-stimulated insulin secretion from islet β cells is mediated by K ATP channels. However, the role of non-K ATP K + channels in insulin secretion is largely unknown. Here, we show that a non-K ATP K + channel, KCNH6, plays a key role in insulin secretion and glucose hemostasis in humans and mice. KCNH6 p.P235L heterozygous mutation co-separated with diabetes in a four-generation pedigree. Kcnh6 knockout (KO) or Kcnh6 p.P235L knockin (KI) mice had a phenotype characterized by changing from hypoglycemia with hyperinsulinemia to hyperglycemia with insulin deficiency. Islets from the young KO mice had increased intracellular calcium concentration and increased insulin secretion. However, islets from the adult KO mice not only had increased intracellular calcium levels but also had remarkable ER stress and apoptosis, associated with loss of β cell mass and decreased insulin secretion. Therefore, dysfunction of KCNH6 causes overstimulation of insulin secretion in the short term and β cell failure in the long term.
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    Journal Title
    Cell Reposrts
    Volume
    25
    Issue
    13
    DOI
    https://doi.org/10.1016/j.celrep.2018.12.005
    Copyright Statement
    © 2018 The Author(s).This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
    Subject
    Biochemistry and cell biology
    Medical physiology
    Science & Technology
    Life Sciences & Biomedicine
    Cell Biology
    PANCREATIC BETA-CELLS
    POTASSIUM CHANNEL
    Publication URI
    http://hdl.handle.net/10072/387085
    Collection
    • Journal articles

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