{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T13:48:37Z","timestamp":1776779317382,"version":"3.51.2"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"vor","delay-in-days":84,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070890"],"award-info":[{"award-number":["82070890"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81930019"],"award-info":[{"award-number":["81930019"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["7232230"],"award-info":[{"award-number":["7232230"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Insulin secretion is mainly regulated by two electrophysiological events, depolarization initiated by the closure of adenosine triphosphate (ATP)-sensitive K+ (KATP) channels and repolarization mediated by K+ efflux. Quinine, a natural component commonly used for the treatment of malaria, has been reported to directly stimulate insulin release and lead to hypoglycemia in patients during treatment through inhibiting KATP channels. In this study, we verified the insulinotropic effect of quinine on the isolated mouse pancreatic islets. We also revealed that low-dose quinine (&amp;lt;20 \u03bcM) did not directly provoke Ca2+ spikes or insulin secretion under low-glucose conditions but potentiated Ca2+ influx and insulin secretion induced by high glucose, which cannot be explained by KATP inhibition. KCNH6 (hERG2) is a voltage-dependent K+ (Kv) channel that plays a critical role in the repolarization of pancreatic \u03b2 cells. Patch clamp experiments showed that quinine inhibited hERG channels at low micromolar concentrations. However, whether quinine can target KCNH6 to potentiate glucose-induced insulin secretion remains unclear. Here, we showed that in vivo administration of low-dose quinine (25\u00a0mg\/kg) improved glucose tolerance and increased glucose-induced insulin release in wild-type control mice but not in Kcnh6-\u03b2-cell-specific knockout (\u03b2KO) mice. Consistently, in vitro treatment of primary islet \u03b2 cells with low-dose quinine (10 \u03bcM) prolonged action potential duration and augmented glucose-induced Ca2+ influx in the wild-type control group but not in the Kcnh6-\u03b2KO group. Our results demonstrate that KCNH6 plays an important role in low-dose quinine-potentiated insulin secretion and provide new insights into KCNH6-targeted drug development.<\/jats:p>","DOI":"10.1093\/jmcb\/mjae051","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T03:03:27Z","timestamp":1737687807000},"source":"Crossref","is-referenced-by-count":2,"title":["Low-dose quinine targets KCNH6 to potentiate glucose-induced insulin secretion"],"prefix":"10.1093","volume":"16","author":[{"given":"Feng-Ran","family":"Xiong","sequence":"first","affiliation":[{"name":"Beijing Diabetes Institute, Beijing Key Laboratory of Diabetes Research and Care, Beijing Tongren Hospital, Capital Medical University Department of Endocrinology, , Beijing 100730 ,","place":["China"]},{"name":"Laboratory for Clinical Medicine, Capital Medical University , Beijing 100069 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan-Juan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Beijing Diabetes Institute, Beijing Key Laboratory of Diabetes Research and Care, Beijing Tongren Hospital, Capital Medical University Department of Endocrinology, , Beijing 100730 ,","place":["China"]},{"name":"Laboratory for Clinical Medicine, Capital Medical University , Beijing 100069 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Rong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Beijing Diabetes Institute, Beijing Key Laboratory of Diabetes Research and Care, Beijing Tongren Hospital, Capital Medical University Department of Endocrinology, , Beijing 100730 ,","place":["China"]},{"name":"Laboratory for Clinical Medicine, Capital Medical University , Beijing 100069 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Lu","sequence":"additional","affiliation":[{"name":"Beijing Diabetes Institute, Beijing Key Laboratory of Diabetes Research and Care, Beijing Tongren Hospital, Capital Medical University Department of Endocrinology, , Beijing 100730 ,","place":["China"]},{"name":"Laboratory for Clinical Medicine, Capital Medical University , Beijing 100069 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5430-2149","authenticated-orcid":false,"given":"Jin-Kui","family":"Yang","sequence":"additional","affiliation":[{"name":"Beijing Diabetes Institute, Beijing Key Laboratory of Diabetes Research and Care, Beijing Tongren Hospital, Capital Medical University Department of Endocrinology, , Beijing 100730 ,","place":["China"]},{"name":"Laboratory for Clinical Medicine, Capital Medical University , Beijing 100069 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,1,23]]},"reference":[{"key":"2025061207312951100_bib1","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/1475-2875-10-144","article-title":"Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria","volume":"10","author":"Achan","year":"2011","journal-title":"Malar. 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