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

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 tha...

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Detalles Bibliográficos
Autores principales: Hastoy, Benoît, Godazgar, Mahdieh, Clark, Anne, Nylander, Vibe, Spiliotis, Ioannis, van de Bunt, Martijn, Chibalina, Margarita V., Barrett, Amy, Burrows, Carla, Tarasov, Andrei I., Scharfmann, Raphael, Gloyn, Anna L., Rorsman, Patrik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6242937/
https://www.ncbi.nlm.nih.gov/pubmed/30451893
http://dx.doi.org/10.1038/s41598-018-34743-7
Descripción
Sumario: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 [Ca(2+)](i), membrane depolarisation and increased action potential firing. Similar to human primary beta cells, K(ATP) channel activity is low at 1 mM glucose and is further reduced upon increasing glucose concentration; an effect that was mimicked by the K(ATP) channel blocker tolbutamide. The upstroke of the action potentials reflects the activation of Ca(2+) channels with some small contribution of TTX-sensitive Na(+) channels. The repolarisation involves activation of voltage-gated Kv2.2 channels and large-conductance Ca(2+)-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.