Role of the AMP kinase in cytokine-induced human EndoC-beta H1 cell death
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
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.
AMPK, ATP, EndoC-beta H1 cells, Cytokines, Apoptosis, NF-kappaB, STAT-1
Endocrinology and Diabetes
IdentifiersURN: urn:nbn:se:uu:diva-264600DOI: 10.1016/j.mce.2015.07.015ISI: 000361263800006PubMedID: 26213325OAI: oai:DiVA.org:uu-264600DiVA: diva2:866072
FunderSwedish Diabetes Association