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 proinsul...

The insulin gene is expressed almost exclusively in the β cells of the islets of Langerhans, where transcriptional control is conferred by cis-acting regulatory sequences located within 300–400 base pairs from the transcription start site. These elements bind β-cell restricted (e.g. PDX-1) and ubiquitous (E47) transcription factors. In non-β cells the insulin gene is localised within tightly packed (hetero) chromatin structures. Developments in under...

The shortage of donor material has driven research towards finding a replenishable supply of islets for transplantation. We have previously shown that the exocrine material that results as a by-product of the islet isolation procedure can be transdifferentiated towards functional islet-like structures by overexpression of the pancreatic transcription factors (TFs) Pdx1, MafA, Ngn3 and Pax4 followed by culture in the presence of betacellulin, nicotinamide and exendin-4. These c...

The endocrine pancreas develops from cells of the endoderm which in response to extracellular signals express the transcription factor PDX1 that subsequently induces formation of the pancreas. At a later stage neurogenin 3 (ngn3) is activated in a sub-set of cells that are then destined to become endocrine cells. The final stage of differentiation to the various cell types of the islets of Langerhans is controlled by a number of transcription factors including PAX4 and PDX1 (i...