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

TitleFrom Hyper- to Hypoinsulinemia and Diabetes: Effect of KCNH6 on Insulin Secretion
Authors
Keywordsmaturity-onset diabetes of the young
MODY
monogenic diabetes
type 2 diabetes
islet
Issue Date2018
PublisherElsevier (Cell Press): OAJ. The Journal's web site is located at http://cell.com/cell-reports
Citation
Cell Reports, 2018, v. 25 n. 13, p. 3800-3810.e6 How to Cite?
AbstractGlucose-stimulated insulin secretion from islet β cells is mediated by KATP channels. However, the role of non-KATP K+ channels in insulin secretion is largely unknown. Here, we show that a non-KATP 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.
Persistent Identifierhttp://hdl.handle.net/10722/273927
ISSN
2019 Impact Factor: 8.109
2015 SCImago Journal Rankings: 8.588
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYang, J-K-
dc.contributor.authorLu, J-
dc.contributor.authorYuan, S-S-
dc.contributor.authorAsan-
dc.contributor.authorShi, T-T-
dc.contributor.authorCao, X-
dc.contributor.authorQiu, HY-
dc.contributor.authorYang, F-Y-
dc.contributor.authorLi, Q-
dc.contributor.authorLiu, C-P-
dc.contributor.authorWu, Q-
dc.contributor.authorWang, YH-
dc.contributor.authorHuang, HX-
dc.contributor.authorKayoumu, A-
dc.contributor.authorFeng, J-P-
dc.contributor.authorXie, R-R-
dc.contributor.authorZhu, X-R-
dc.contributor.authorLiu, C-
dc.contributor.authorYang, G-R-
dc.contributor.authorZhang, MR-
dc.contributor.authorXie, CL-
dc.contributor.authorChen, C-
dc.contributor.authorZhang, B-
dc.contributor.authorLiu, G-
dc.contributor.authorZhang, XQ-
dc.contributor.authorXu, A-
dc.date.accessioned2019-08-18T14:51:29Z-
dc.date.available2019-08-18T14:51:29Z-
dc.date.issued2018-
dc.identifier.citationCell Reports, 2018, v. 25 n. 13, p. 3800-3810.e6-
dc.identifier.issn2211-1247-
dc.identifier.urihttp://hdl.handle.net/10722/273927-
dc.description.abstractGlucose-stimulated insulin secretion from islet β cells is mediated by KATP channels. However, the role of non-KATP K+ channels in insulin secretion is largely unknown. Here, we show that a non-KATP 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.-
dc.languageeng-
dc.publisherElsevier (Cell Press): OAJ. The Journal's web site is located at http://cell.com/cell-reports-
dc.relation.ispartofCell Reports-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectmaturity-onset diabetes of the young-
dc.subjectMODY-
dc.subjectmonogenic diabetes-
dc.subjecttype 2 diabetes-
dc.subjectislet-
dc.titleFrom Hyper- to Hypoinsulinemia and Diabetes: Effect of KCNH6 on Insulin Secretion-
dc.typeArticle-
dc.identifier.emailXu, A: amxu@hkucc.hku.hk-
dc.identifier.authorityXu, A=rp00485-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.celrep.2018.12.005-
dc.identifier.pmid30590050-
dc.identifier.hkuros301578-
dc.identifier.volume25-
dc.identifier.issue13-
dc.identifier.spage3800-
dc.identifier.epage3810.e6-
dc.identifier.isiWOS:000454437100020-
dc.publisher.placeUnited States-

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