Role of the AMP kinase in cytokine-induced human EndoC-βH1 cell death.

Fred RG, Kappe C, Ameur A, Cen J, Bergsten P, Ravassard P, Scharfmann R, Welsh N

Mol. Cell. Endocrinol. 414 (-) 53-63 [2015-10-15; online 2015-07-26]

The aim of the present investigation was to delineate cytokine-induced signaling and death using the EndoC-βH1 cells as a model for primary human beta-cells. The cytokines IL-1β and IFN-γ induced a rapid and transient activation of NF-κB, STAT-1, ERK, JNK and eIF-2α signaling. The EndoC-βH1 cells died rapidly when exposed to IL-1β + IFN-γ, and this occurred also in the presence of the actinomycin D. Inhibition of NF-κB and STAT-1 did not protect against cell death, nor did the cytokines activate iNOS expression. Instead, cytokines promoted a rapid decrease in EndoC-βH1 cell respiration and ATP levels, and we observed protection by the AMPK activator AICAR against cytokine-induced cell death. It is concluded that EndoC-βH1 cell death can be prevented by AMPK activation, which suggests a role for ATP depletion in cytokine-induced human beta-cell death.

Affiliated researcher

PubMed 26213325

DOI 10.1016/j.mce.2015.07.015

Crossref 10.1016/j.mce.2015.07.015

pii: S0303-7207(15)30024-1


Publications 7.2.9