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- Publisher Website: 10.1016/j.celrep.2018.12.005
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Article: From Hyper- to Hypoinsulinemia and Diabetes: Effect of KCNH6 on Insulin Secretion
Title | From Hyper- to Hypoinsulinemia and Diabetes: Effect of KCNH6 on Insulin Secretion |
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Authors | |
Keywords | maturity-onset diabetes of the young MODY monogenic diabetes type 2 diabetes islet |
Issue Date | 2018 |
Publisher | Elsevier (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? |
Abstract | Glucose-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 Identifier | http://hdl.handle.net/10722/273927 |
ISSN | 2023 Impact Factor: 7.5 2023 SCImago Journal Rankings: 4.279 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Yang, J-K | - |
dc.contributor.author | Lu, J | - |
dc.contributor.author | Yuan, S-S | - |
dc.contributor.author | Asan | - |
dc.contributor.author | Shi, T-T | - |
dc.contributor.author | Cao, X | - |
dc.contributor.author | Qiu, HY | - |
dc.contributor.author | Yang, F-Y | - |
dc.contributor.author | Li, Q | - |
dc.contributor.author | Liu, C-P | - |
dc.contributor.author | Wu, Q | - |
dc.contributor.author | Wang, YH | - |
dc.contributor.author | Huang, HX | - |
dc.contributor.author | Kayoumu, A | - |
dc.contributor.author | Feng, J-P | - |
dc.contributor.author | Xie, R-R | - |
dc.contributor.author | Zhu, X-R | - |
dc.contributor.author | Liu, C | - |
dc.contributor.author | Yang, G-R | - |
dc.contributor.author | Zhang, MR | - |
dc.contributor.author | Xie, CL | - |
dc.contributor.author | Chen, C | - |
dc.contributor.author | Zhang, B | - |
dc.contributor.author | Liu, G | - |
dc.contributor.author | Zhang, XQ | - |
dc.contributor.author | Xu, A | - |
dc.date.accessioned | 2019-08-18T14:51:29Z | - |
dc.date.available | 2019-08-18T14:51:29Z | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | Cell Reports, 2018, v. 25 n. 13, p. 3800-3810.e6 | - |
dc.identifier.issn | 2211-1247 | - |
dc.identifier.uri | http://hdl.handle.net/10722/273927 | - |
dc.description.abstract | Glucose-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.language | eng | - |
dc.publisher | Elsevier (Cell Press): OAJ. The Journal's web site is located at http://cell.com/cell-reports | - |
dc.relation.ispartof | Cell Reports | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | maturity-onset diabetes of the young | - |
dc.subject | MODY | - |
dc.subject | monogenic diabetes | - |
dc.subject | type 2 diabetes | - |
dc.subject | islet | - |
dc.title | From Hyper- to Hypoinsulinemia and Diabetes: Effect of KCNH6 on Insulin Secretion | - |
dc.type | Article | - |
dc.identifier.email | Xu, A: amxu@hkucc.hku.hk | - |
dc.identifier.authority | Xu, A=rp00485 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1016/j.celrep.2018.12.005 | - |
dc.identifier.pmid | 30590050 | - |
dc.identifier.scopus | eid_2-s2.0-85058629021 | - |
dc.identifier.hkuros | 301578 | - |
dc.identifier.volume | 25 | - |
dc.identifier.issue | 13 | - |
dc.identifier.spage | 3800 | - |
dc.identifier.epage | 3810.e6 | - |
dc.identifier.isi | WOS:000454437100020 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 2211-1247 | - |