Desarrollo de estrategias de terapia génica para diabetes tipo 1 y 2.

The general hypothesis of this project is that by using genetic engineering techniques a more appopriate therapy for type 1 and 2 diabetes mellitus might be achieved. These new approaches might delay or even avoid the development of the secondary complications of this disease. The main objective of this project is centered in developing gene therapy approaches for typr 2 diabetes by genetic manipulation of the liver or skeletal muscle, and for type 1 diabetes by regeneration of pancreatic islets in vivo. This objective involves: 1)To study the capacity to decrease type 2 diabetic hyperglycemia by increasing glucose uptake by the liver or skeletal muscle. 2) To establish a new therapeutical approach for type 1 diabetes by endocrine pancreas regeneration. To this end, the following studies will be carried out: a) In type 2 diabetic mice after c-myc gene transfer to the liver or glucokinase and/or uncoupling proteins to skeletal muscle by using viral (adenovirus (AV) or adenoassociated virus (AAV) and non-viral vectors. b) In type 1 diabetic mice and dogs by IGF-I, VEGF or HGF gene transfer to pancreas in vivo using AV,AAV or lentiviral vectors. The results of this project will probably constitute a step forward to a more effective therapy for both type 1 and type 2 diabetes mellitus.