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 beta-cells and deposition of islet amyloid derived from islet amyloid polypeptide (IAPP). We have previously demonstrated that IAPP -derived amyloid forms intracellularly in humans with chronic excess i nsulin expression (eg, insulinoma and insulin receptor antibody-induce d insulin resistance). To determine whether overexpression of IAPP res ults in intracellular amyloid in mammalian cells, we transfected COS c ells with vectors expressing amyloidogenic human IAPP or non-amyloidog enic rat IAPP. Transfected COS-1 cells secreted comparable amounts of human IAPP and rat IAPP (2.1 to 28 nmol/L/48 hours). After 96 hours, 9 0% of cells expressing human IAPP contained amyloid fibrils and were d egenerating or dead, whereas cells transfected with rat IAPP lacked am yloid and were viable. Thus, overexpression of human IAPP can result i n intracellular amyloid formation that is associated with cell death, suggesting that intracellular amyloid may play a role in beta-cell los s in non-insulin-dependent diabetes mellitus.