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Role of the AMP kinase in cytokine-induced human EndoC-beta H1 cell death
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0001-6085-6749
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
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2015 (English)In: Molecular and Cellular Endocrinology, ISSN 0303-7207, E-ISSN 1872-8057, Vol. 414, no C, 53-63 p.Article in journal (Refereed) Published
Abstract [en]

The aim of the present investigation was to delineate cytokine-induced signaling and death using the EndoC-beta H1 cells as a model for primary human beta-cells. The cytokines IL-1 beta and IFN-gamma induced a rapid and transient activation of NF-kappa B, STAT-1, ERK, JNK and eIF-2 alpha signaling. The EndoC-beta H1 cells died rapidly when exposed to IL-1 beta + IFN-gamma, and this occurred also in the presence of the actinomycin D. Inhibition of NF-kappa B and STAT-1 did not protect against cell death, nor did the cytokines activate iNOS expression. Instead, cytokines promoted a rapid decrease in EndoC-beta H1 cell respiration and ATP levels, and we observed protection by the AMPK activator AICAR against cytokine-induced cell death. It is concluded that EndoC-beta H1 cell death can be prevented by AMPK activation, which suggests a role for ATP depletion in cytokine-induced human beta-cell death.

Place, publisher, year, edition, pages
2015. Vol. 414, no C, 53-63 p.
Keyword [en]
AMPK, ATP, EndoC-beta H1 cells, Cytokines, Apoptosis, NF-kappaB, STAT-1
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:uu:diva-264600DOI: 10.1016/j.mce.2015.07.015ISI: 000361263800006PubMedID: 26213325OAI: oai:DiVA.org:uu-264600DiVA: diva2:866072
Funder
Swedish Diabetes Association
Available from: 2015-10-30 Created: 2015-10-15 Last updated: 2017-12-01Bibliographically approved

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Fred, Rikard G.Kappe, CamillaAmeur, AdamBergsten, PeterWelsh, Nils

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