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Electrophysiological properties of human beta-cell lines EndoC-beta H1 and -beta H2 conform with human beta-cells

Artikel i vetenskaplig tidskrift
Författare B. Hastoy
M. Godazgar
A. Clark
V. Nylander
I. Spiliotis
M. van de Bunt
M. V. Chibalina
A. Barrett
C. Burrows
A. I. Tarasov
R. Scharfmann
A. L. Gloyn
Patrik Rorsman
Publicerad i Scientific Reports
Volym 8
ISSN 2045-2322
Publiceringsår 2018
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi
Språk en
Länkar dx.doi.org/10.1038/s41598-018-34743...
Ämnesord insulin-secretion, glucose, responses, Science & Technology - Other Topics, an pm, 1973, diabetologia, v9, p115
Ämneskategorier Klinisk fysiologi

Sammanfattning

Limited access to human islets has prompted the development of human beta cell models. The human beta cell lines EndoC-beta H1 and EndoC-beta H2 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, K-ATP channel activity is low at 1mM 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 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 electrondense core surrounded by a thin clear halo. We conclude that the EndoC-beta H1 and -beta H2 cells share many features of primary human beta-cells and thus represent a useful experimental model.

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