UROP Research Mentor Project Submission Portal: Submission #1115

Overall Research Project Description Insulin-derived amyloidosis (“insulin balls”) develops at sites of repeated subcutaneous insulin injection and can impair insulin absorption and glycemic control. However, the cellular mechanisms that allow these deposits to persist remain poorly understood. We hypothesize that when macrophages phagocytose insulin amyloid, the fibrils inflict both physical and chemical damage to phagosomal membranes, resulting in lysosomal dysfunction and pro-inflammatory signaling that impairs clearance. To investigate this, we will employ a novel approach to synthesize insulin amyloid aggregates with precisely defined compositions and structures, enabling controlled studies of their interactions with model macrophages. Our research has two primary objectives: (1) to optimize methods for producing synthetic insulin amyloids with reproducible properties, and (2) to determine whether these aggregates cause measurable phagosomal damage in macrophages. By elucidating the mechanisms underlying insulin amyloid–induced cellular injury, this work aims to provide new insights into the pathogenesis of insulin-derived amyloidosis and to inform strategies for preventing or mitigating these lesions in diabetes management.