Finally, HMGB1, an immunological activating protein [23], is released in β-cells exposed to IL-1β, but not to the topoisomerase inhibitor CPT or the general protein kinase inhibitor STS (both genuine inducers of apoptosis) [9]; activation of the immune system by necrotic release of immuno-stimulatory molecules is also consistent with the insulitis and immune cell recruitment to pancreatic islets that leads to T1DM. Here, PROS1 is linked to type 1 diabetes mellitus.