A loss of ?-cell mass and biologically active insulin is a key feature of both type 1 and type 2 diabetes. Thus, increasing ?-cell mass, for example with small molecules, has become an area of major research interest in the diabetes community. Our groups have recently reported the discovery of small molecules capable of inducing human ?-cell proliferation; however, the potential for inducing wide-ranging proliferation across multiple tissues and cell types makes such an approach risky. Here, we aim to develop a zinc-based prodrug (ZnPD) system for targeted ?-cell delivery of small molecules that promote ?-cell proliferation. This system will enable us to perform early-stage preclinical validation that selective ?-cell delivery will be safer and more effective than nonselective systemic administration.
Diabetes is characterized by dysfunction and death of insulin-producing beta cells. Small molecules that promote beta-cell proliferation are useful tools for regenerative medicine, but it is imperative that such compounds act selectively on beta cells. We propose to develop general methods and reagents for targeted release of small molecules to beta cells in vivo using principles and techniques from chemical biology.
