Use of a systems biology approach to understand pancreatic beta-cell death in Type 1 diabetes.

Accumulating evidence indicates that beta-cells die by apoptosis in T1DM (Type 1 diabetes mellitus). Apoptosis is an active gene-directed process, and recent observations suggest that beta-cell apoptosis depends on the parallel and/or sequential up- and down-regulation of hundreds of genes controlled by key transcription factors such as NF-kappaB (nuclear factor kappaB) and STAT-1 (signal transducer and activator of transcription 1). Understanding the regulation of these gene networks, and how they modulate beta-cell death and the 'dialogue' between beta-cells and the immune system, will require a systems biology approach to the problem. This will hopefully allow the search for a cure for T1DM to move from a 'trial-and-error' approach to one that is really mechanistically driven.