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dc.contributor.authorZhao, MM
dc.contributor.authorLu, J
dc.contributor.authorLi, S
dc.contributor.authorWang, H
dc.contributor.authorCao, X
dc.contributor.authorLi, Q
dc.contributor.authorShi, TT
dc.contributor.authorMatsunaga, K
dc.contributor.authorChen, C
dc.contributor.authorHuang, H
dc.contributor.authorIzumi, T
dc.contributor.authorYang, JK
dc.date.accessioned2021-10-07T00:44:40Z
dc.date.available2021-10-07T00:44:40Z
dc.date.issued2021
dc.identifier.issn2041-1723
dc.identifier.doi10.1038/s41467-021-25952-2
dc.identifier.urihttp://hdl.handle.net/10072/408674
dc.description.abstractCoptis chinensis is an ancient Chinese herb treating diabetes in China for thousands of years. However, its underlying mechanism remains poorly understood. Here, we report the effects of its main active component, berberine (BBR), on stimulating insulin secretion. In mice with hyperglycemia induced by a high-fat diet, BBR significantly increases insulin secretion and reduced blood glucose levels. However, in mice with hyperglycemia induced by global or pancreatic islet β-cell-specific Kcnh6 knockout, BBR does not exert beneficial effects. BBR directly binds KCNH6 potassium channels, significantly accelerates channel closure, and subsequently reduces KCNH6 currents. Consequently, blocking KCNH6 currents prolongs high glucose-dependent cell membrane depolarization and increases insulin secretion. Finally, to assess the effect of BBR on insulin secretion in humans, a randomized, double-blind, placebo-controlled, two-period crossover, single-dose, phase 1 clinical trial (NCT03972215) including 15 healthy men receiving a 160-min hyperglycemic clamp experiment is performed. The pre-specified primary outcomes are assessment of the differences of serum insulin and C-peptide levels between BBR and placebo treatment groups during the hyperglycemic clamp study. BBR significantly promotes insulin secretion under hyperglycemic state comparing with placebo treatment, while does not affect basal insulin secretion in humans. All subjects tolerate BBR well, and we observe no side effects in the 14-day follow up period. In this study, we identify BBR as a glucose-dependent insulin secretagogue for treating diabetes without causing hypoglycemia that targets KCNH6 channels.
dc.description.peerreviewedYes
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.relation.ispartofpagefrom5616
dc.relation.ispartofissue1
dc.relation.ispartofjournalNature Communications
dc.relation.ispartofvolume12
dc.subject.fieldofresearchEndocrinology
dc.subject.fieldofresearchClinical sciences
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchcode320208
dc.subject.fieldofresearchcode3202
dc.subject.fieldofresearchcode3214
dc.titleBerberine is an insulin secretagogue targeting the KCNH6 potassium channel
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationZhao, MM; Lu, J; Li, S; Wang, H; Cao, X; Li, Q; Shi, TT; Matsunaga, K; Chen, C; Huang, H; Izumi, T; Yang, JK, Berberine is an insulin secretagogue targeting the KCNH6 potassium channel, Nature Communications, 2021, 12 (1), pp. 5616
dcterms.dateAccepted2021-09-08
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.date.updated2021-10-07T00:18:29Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
gro.hasfulltextFull Text
gro.griffith.authorChen, Chen


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