Pathogenesis of fulminant type1 diabetes: Genes, viruses and the immune mechanism, and usefulness of patient-derived induced pluripotent stem cells for future research.

Abstract

We reviewed fulminant type 1 diabetes, a recently established subtype of type 1 diabetes, from the aspects of genes, viruses, immune mechanism and usefulness of patient‐derived induced pluripotent stem cells (iPSCs). In an analysis of the pancreas of patients with fulminant type 1 diabetes, viral antigens and viral receptors were expressed in β‐cells, as well as macrophages and T lymphocytes surrounding the β‐cells. These findings suggest that the β‐cells of patients with fulminant type 1 diabetes are destroyed during an immune response against viral infection of the pancreas. Recently, fulminant type 1 diabetes was induced by treatment with anti‐programmed cell death 1 antibodies, suggesting that immune regulatory mechanisms are also involved in the onset of this disease. We generated iPSCs from patients with fulminant type 1 diabetes for the first time. We also successfully differentiated patient‐derived iPSCs into insulin‐producing cells in vitro, and produced a disease model. The proportion of cytokine‐induced apoptotic cells among insulin‐positive cells was higher in the iPSCs from patients with fulminant type 1 diabetes than in iPSCs from healthy control participants. We carried out ribonucleic acid sequencing in insulin‐producing cells differentiated from patient‐derived iPSCs, and are now attempting to identify new biomarkers for the disease.