Abstract

Diabetes is a metabolic disorder in which high blood glucose levels persist over a prolonged period. All types of diabetes are caused by a profound loss of insulin producing beta-cells, insufficient insulin production or a compromised insulin response in key tissue. Remarkably, transplantation of cadaveric beta-cells into the liver of has demonstrates that diabetic patients, particularly those with severe beta-cell loss, can be cured by beta-cell transplantation into tissue outside the pancreas, where beta-cells normally reside. In vivo cell lineage reprogramming represents as a novel strategy to directly produce new, functional replacement beta-cells within the body. While in vivo reprogramming has been successfully used to ameliorate high blood glucose in diabetic animal models, the cell types that have been targeted for in vivo cell reprogramming have been limited to the gut endoderm, particularly cells of the pancreas and liver. This may be problematic because conversion of large numbers of cells within these essential organs may compromise their function, potentially exacerbating the disease. Our lab has recently discovered factors that function in vivo to convert completely unrelated cells, including muscle and skin cells into precursor cells that normally go on to become beta-cells. We now seek to leverage our breakthrough to identify other specification factors and useful chemicals that will push further our induced pancreatic progenitors toward functional beta cells directly in vivo.