Aims/hypothesis
Beta cell destruction in type 1 diabetes is apparently mediated by the release of cytokines. We questioned whether cytokine-induced
apoptosis preferentially kills replicating beta cells.
Materials and methods
In the first experiment, rat insulinoma (RIN) cells were studied for 36 h by time-lapse video microscopy. Cells were exposed
to three doses of a cytokine mixture (maximal concentration: IL-1β 50 U/ml; TNF-α 1,000 U/ml; IFN-γ 1,000 U/ml) or vehicle
and analysed for the total cell number (2-h intervals) and timing of each cell death and division. In the second experiment,
isolated human islets were incubated with the same cytokine mixture for 24 h and examined for replication and paired (postmitotic)
apoptosis.
Results
In the first experiment, after application of cytokines, apoptosis occurred most frequently immediately after the next or
subsequent cell mitosis (p<0.05). In the second experiment, cytokines caused increased apoptosis in human islets, with an increase in the proportion
of postmitotic apoptotic pairs (p<0.001).
Conclusions/interpretation
Cytokine-induced beta cell death preferentially affects newly forming beta cells, which implies that replicating beta cells
might be more vulnerable to cytokine destruction. Efforts to expand beta cell mass in type 1 diabetes by fostering beta cell
replication are likely to fail unless cytokine-induced apoptosis is concurrently suppressed.
Keywords Apoptosis - Beta cell - Cell death - Cytokines - Postmitotic apoptosis - Replication - Type 1 diabetes