Grant: CIHR REDI Early Career Transition Award - Type 1 Diabetes: III

Pancreatic beta cells produce insulin, a hormone, to control blood glucose levels. On the molecular level, insulin is first generated as a larger precursor protein called proinsulin. Through a stepwise enzyme-mediated conversion in beta cells, proinsulin is processed into the smaller and more biologically active insulin. In beta cells of subjects with type 1 diabetes (T1D), the conversion of proinsulin to insulin is impaired, leading to the accumulation of proinsulin. We and others have recently found that, other precursor hormones are also elevated in the beta cells of subjects with T1D. We plan to determine whether increased precursor hormones in beta cells contributes to cellular abnormalities and activates immune cells (which target and destroy beta cells), in preclinical animal models of T1D.