Electrophysiological properties of human beta-cell lines EndoC-βH1 and -βH2 conform with human beta-cells

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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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.

Original languageEnglish
Article number16994
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

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    Hastoy, B., Godazgar, M., Clark, A., Nylander, V., Spiliotis, I., van de Bunt, M., Chibalina, M. V., Barrett, A., Burrows, C., Tarasov, A. I., Scharfmann, R., Gloyn, A. L., & Rorsman, P. (2018). Electrophysiological properties of human beta-cell lines EndoC-βH1 and -βH2 conform with human beta-cells. Scientific Reports, 8(1), [16994]. https://doi.org/10.1038/s41598-018-34743-7