University of Hertfordshire

Documents

  • Benoît Hastoy
  • Mahdieh Godazgar
  • Anne Clark
  • Vibe Nylander
  • Ioannis Spiliotis
  • Martijn van de Bunt
  • Margarita V Chibalina
  • Amy Barrett
  • Carla Burrows
  • Andrei I Tarasov
  • Raphael Scharfmann
  • Anna L Gloyn
  • Patrik Rorsman
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Original languageEnglish
Article number16994
Pages (from-to)1-16
JournalScientific Reports
Journal publication date19 Nov 2018
Volume8
Issue1
DOIs
Publication statusPublished - 19 Nov 2018

Abstract

Limited access to human islets has prompted the development of human beta cell models. The human beta cell lines EndoC-βH1 and EndoC-βH2 are increasingly used by the research community. However, little is known of their electrophysiological and secretory properties. Here, we monitored parameters that constitute the glucose-triggering pathway of insulin release. Both cell lines respond to glucose (6 and 20 mM) with 2- to 3-fold stimulation of insulin secretion which correlated with an elevation of [Ca2+]i, membrane depolarisation and increased action potential firing. Similar to human primary beta cells, KATP channel activity is low at 1 mM glucose and is further reduced upon increasing glucose concentration; an effect that was mimicked by the KATP channel blocker tolbutamide. The upstroke of the action potentials reflects the activation of Ca2+ channels with some small contribution of TTX-sensitive Na+ channels. The repolarisation involves activation of voltage-gated Kv2.2 channels and large-conductance Ca2+-activated K+ channels. Exocytosis presented a similar kinetics to human primary beta cells. The ultrastructure of these cells shows insulin vesicles composed of an electron-dense core surrounded by a thin clear halo. We conclude that the EndoC-βH1 and -βH2 cells share many features of primary human β-cells and thus represent a useful experimental model.

Notes

© The Author(s) 2018

ID: 15699077