Aproximacions a la teràpia gènica de la diabetis.

Diabetes mellitus is the most common metabolic disease in humans. All forms of diabetes are characterized by hyperglycemia, which is supposed to be a main cause in the development of diabetes-specific microvascular pathology in retina and kidney, and neurological complications. Diabetes also increases the risk of early atherosclerosis, and cardiovascular and cerebrovascular complications. Insulin administration cannot prevent the severe secondary complications of the disease. The aim of this project is to achieve regulated expression of insulin in extrapancreatic tissues, which should be able to correct diabetic alterations. To this end, different chimeric genes targeting the expression to the liver and adipose tissue (-2000PEPCK promoter), or to skeletal muscle (PEPCK-MLC chimeric promoter) will be obtained. These genes will be transfered to animals by embryo microinjection, and to cells using retroviral vectors. Engineered cells to produce insulin will be transplanted back to diabetic animals. Both approaches will provide new insights in the design of an artificial beta-cell. In conclusion, the results from this study will be useful for developement of gene therapy protocols in humans.