2. Academic Validation
  3. Inhibition of voltage-gated K+ channels mediates docosahexaenoic acid-stimulated insulin secretion in rat pancreatic β-cells

Inhibition of voltage-gated K+ channels mediates docosahexaenoic acid-stimulated insulin secretion in rat pancreatic β-cells

  • Food Funct. 2020 Oct 21;11(10):8893-8904. doi: 10.1039/d0fo01891k.
Tao Bai 1,  Huanhuan Yang 2,  Hui Wang 2,  Linping Zhi 2,  Tao Liu 3,  Lijuan Cui 3,  Wen Liu 4,  Yan Wang 2,  Min Zhang 5,  Yunfeng Liu 6,  Yi Zhang 3
Affiliations

Affiliations

  • 1 Department of Pharmacology, Shanxi Medical University, Taiyuan, Shanxi 030001, P. R. China. baitaoy@163.com 18306082675@163.com 1074684265@qq.com 2816450758@qq.com ltwj8182@163.com c.h.clj@sina.com butou1977@163.com yizhang313@163.com and Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, P. R. China and Department of Endocrinology, the First Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan, Shanxi 030001, P. R. China. nectarliu@163.com.
  • 2 Department of Pharmacology, Shanxi Medical University, Taiyuan, Shanxi 030001, P. R. China. baitaoy@163.com 18306082675@163.com 1074684265@qq.com 2816450758@qq.com ltwj8182@163.com c.h.clj@sina.com butou1977@163.com yizhang313@163.com.
  • 3 Department of Pharmacology, Shanxi Medical University, Taiyuan, Shanxi 030001, P. R. China. baitaoy@163.com 18306082675@163.com 1074684265@qq.com 2816450758@qq.com ltwj8182@163.com c.h.clj@sina.com butou1977@163.com yizhang313@163.com and Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, P. R. China.
  • 4 Department of Chemistry, Shanxi Medical University, Taiyuan, Shanxi 030001, P. R. China. liuwen@sxmu.edu.cn.
  • 5 Department of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi 030001, P. R. China. zmsxmu@126.com.
  • 6 Department of Endocrinology, the First Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan, Shanxi 030001, P. R. China. nectarliu@163.com.
PMID: 32986050 DOI: 10.1039/d0fo01891k
Abstract

Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, plays an important role in regulating glucose metabolism. The aim of this study was to investigate the effect of DHA on Insulin secretion and the underlying ion channel mechanism in rat pancreatic β-cells. The Insulin secretion results illustrated that DHA promoted Insulin secretion in a glucose-dependent manner. Calcium-imaging analysis indicated that DHA elevated intracellular Ca2+ concentration. Using the patch-clamp technique, we found that DHA prolonged the action potential duration (APD) and significantly inhibited voltage-dependent K+ (KV) channels, but did not act directly on voltage-gated Ca2+ channels. Furthermore, our data demonstrate that the insulinotropic effect of DHA was mediated by G protein-coupled receptor 40 (GPR40) as well as the adenylyl cyclase (AC)/cyclic adenosine monophosphate (cAMP)/phospholipase-C (PLC) signaling pathway. Together, these findings illustrate that KV channels play a vital role in DHA-augmented Insulin secretion through a mechanism whereby DHA blocks KV channels via GPR40 and the AC/cAMP/PLC signaling pathway in rat pancreatic β-cells.

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