Miao-Miao Zhao1,2, Jing Lu1,2, Sen Li2, Hao Wang1,2,3, Xi Cao1,2, Qi Li2, Ting-Ting Shi1,2, Kohichi Matsunaga3, Chen Chen4, Huang Haixia5, Tetsuro Izumi3, and Jin-Kui Yang1,2 1Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University. 2Beijing Key Laboratory of Diabetes Research and Care, Beijing Diabetes Institute. 3Laboratory of Molecular Endocrinology and Metabolism, Department of Molecular Medicine, Institute for Molecular and Cellular Regulation, Gunma University. 4School of Biomedical Sciences, University of Queensland. 5Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University.
About
Coptis 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 increased insulin secretion and reduced blood glucose levels. However, in mice with hyperglycemia induced by global or pancreatic islet β-cell-specific Kcnh6 knockout, BBR did not exert beneficial effects. BBR directly bound KCNH6 potassium channels, significantly accelerated channel closure, and subsequently reduced KCNH6 currents. Consequently, blocking KCNH6 currents prolonged high glucose-dependent cell membrane depolarization and increased insulin secretion. Finally, a phase 1 clinical trial in humans using the hyperglycemic clamp technique confirmed the effect of BBR on insulin secretion. In this study, we identify BBR as a new glucose-dependent insulin secretagogue for treating diabetes without causing hypoglycemia that targets KCNH6 channels.
Berberine accelerates closure of KCNH6 potassium channels, and prolongs high glucose-dependent cell membrane depolarization to increase insulin secretion.
Paper information
Zhao M-M, Lu J, Li S, Wang H, Cao X, Li Q, Shi T-T, Matsunaga K, Chen C, Huang H, Izumi T, and Yang J-K (2021). Berberine is an insulin secretagogue targeting the KCNH6 potassium channel. Nat. Commun. 2021 Sep 23;12(1):5616. （doi: 10.1038/s41467-021-25952-2）
Online URL
https://pubmed.ncbi.nlm.nih.gov/34556670/
