Endocrine Abstracts

An increased understanding of the DNA sequences and transcription factors (TFs) involved in regulating expression of the insulin gene, and the role that these TFs play in the developing pancreas has opened up new prospects for cell and gene therapy for diabetes. Gene therapy involves injection of an insulin gene construct into muscle, chosen as the most accessible tissue. The major challenges are efficiency of uptake and expression of the exogenous gene, processing of proinsulin to insulin, and regulated release in response to changes in circulating glucose levels. Efforts are also underway to generate islets that can be used to overcome the paucity of donor material for transplantation. Such cell therapy approaches include deriving functional islets from embryonic stem (ES) cells, and reprogramming of exocrine pancreatic tissue. Protocols are now widely available for deriving islet-like structures from ES cells and clinical trials are currently underway. ES-derived islets can also provide insights and models for human islet development and a major academic facility is available within the UK. Islets can also be generated from the exocrine tissue that is left over from the islet isolation procedure. This is based on the now accepted ability of (TFs) to reprogramme a variety of adult cell types for therapeutic purposes.