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Diabetologia

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27.07.2016 | Article

Sensitivity profile of the human EndoC-βH1 beta cell line to proinflammatory cytokines

verfasst von: Ewa Gurgul-Convey, Ilir Mehmeti, Thomas Plötz, Anne Jörns, Sigurd Lenzen

Erschienen in: Diabetologia | Ausgabe 10/2016

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Abstract

Aims/hypothesis

The aim of this study was to perform a detailed analysis of cytokine toxicity in the new human EndoC-βH1 beta cell line.

Methods

The expression profile of the antioxidative enzymes in the new human EndoC-βH1 beta cells was characterised and compared with that of primary beta cells in the human pancreas. The effects of proinflammatory cytokines on reactive oxygen species formation, insulin secretory responsiveness and apoptosis of EndoC-βH1 beta cells were determined.

Results

EndoC-βH1 beta cells were sensitive to the toxic action of proinflammatory cytokines. Glucose-dependent stimulation of insulin secretion and an increase in the ATP/ADP ratio was abolished by proinflammatory cytokines without induction of IL-1β expression. Cytokine-mediated caspase-3 activation was accompanied by reactive oxygen species formation and developed more slowly than in rodent beta cells. Cytokines transiently increased the expression of unfolded protein response genes, without inducing endoplasmic reticulum stress-marker genes. Cytokine-mediated NFκB activation was too weak to induce inducible nitric oxide synthase expression. The resultant lack of nitric oxide generation in EndoC-βH1 cells, in contrast to rodent beta cells, makes these cells dependent on exogenously generated nitric oxide, which is released from infiltrating immune cells in human type 1 diabetes, for full expression of proinflammatory cytokine toxicity.

Conclusions/interpretation

EndoC-βH1 beta cells are characterised by an imbalance between H₂O₂-generating and -inactivating enzymes, and react to cytokine exposure in a similar manner to primary human beta cells. They are a suitable beta cell surrogate for cytokine-toxicity studies.

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Titel: Sensitivity profile of the human EndoC-βH1 beta cell line to proinflammatory cytokines
verfasst von: Ewa Gurgul-Convey
Ilir Mehmeti
Thomas Plötz
Anne Jörns
Sigurd Lenzen
Publikationsdatum: 27.07.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 10/2016
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-016-4060-y

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Sensitivity profile of the human EndoC-βH1 beta cell line to proinflammatory cytokines

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