Mechanisms and techniques of reprogramming – Using PDX-1 homeobox protein as a novel treatment of insulin dependent diabetes mellitus

Homeobox proteins are key regulators of stem cell proliferation and differentiation which function as transcription factors and regulate cell fate decisions. Pancreatic Duodenal Homeobox-1 (PDX-1) is a homeobox protein which acts as a key regulator in the development of b cells in the Islets of Langerhans. It plays an important role in maintaining the identity and function of the Islets of Langerhans, and in the development of the pancreas. There is strong evidence that PDX-1 plays a role in activating the insulin promoter and increasing insulin levels in response to glucose. PDX-1 also binds to sequences within β cells and regulates the promoter activity of a number of islet genes including insulin, glut-2 and neurogenin 3. When fused with the VP16 activation sequence, transfection of the PDX-1 gene has been shown to transform liver cells into insulin producing cells.Because homeobox proteins are able to passively translocate through cell membranes, due to an intrinsic transduction domain (penetratin), the use of these proteins to reprogram target cells may help overcome the limiting supply of β cells and be a potential future treatment for Type 1 diabetes.