Human islet amyloid polypeptide expression in COS-1 cells: A model of intracellular amyloidogenesis

Non-insulin-dependent diabetes mellitus is characterized by concurrent loss of β-cells and deposition of islet amyloid derived from islet amyloid polypeptide (IAPP). We have previously demonstrated that AP-derived amyloid forms intracellularly in human with chronic excess insulin expression (eg, insulinoma and insulin receptor antibody-induced insulin resistance). To determine whether overexpression of AP results in intracellular amyloid in mammalian cells, we transfected COS cells with vectors expressing amyloidogenic human IAPP or non-amyloidogenic rat IAPP. Transfected COS-1 cells secreted comparable amounts of human AP and rat IAPP (2.1 to 2.8 nmol/L/48 hours). After 96 hours, 90% of cells expressing human IAPP contained amyloid fibrils and were degenerating or dead, whereas cells transfected with rat IAPP lacked amyloid and were viable. Thus, overexpression of human IAPP can result in intracellular amyloid formation that is associated with cell death, suggesting that intracellular amyloid may play a role in β-cell loss in non-insulin-dependent diabetes mellitus.