Electrophysiological properties of human beta-cell lines EndoC-beta H1 and -beta H2 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-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.