All forms of diabetes are characterized by hyperglycemia, development o diabetes-specific microvascular pathology and macrovascular complications. For example, as a consequence of the microvascular pathology, diabetes is now the leading cause of adult blindness. Until now, a clear understanding of the basic pathogenic mechanisms of diabetes has not yet emerged, but the generation of transgenic animal models may give the key to curing the disease.
Fatima Bosch's group has recently obtained transgenic mice that express IGF-I in pancreatic beta-cells. Preliminary results indicate that these animals are diabetic. In addition, these mice develop the long-term complications of the disease (cataracts, glaucoma, retinopathy). These mice constitute the first animal model that naturally develops ocular complications of diabetes mellitus.
In this project, using these transgenic mice, I will study the role of IGF-I in the pathogenesis of diabetes mellitus and the mechanisms leading to development of secondary complications. Furthermore, it has been described that IGF-II, like IGF-I, is able to suppress insulin release. I will obtain another transgenic animal model, overexpressing IGF-II in beta-cells, to study if this factor is also able to alter insulin secretion in vivo and lead to diabetic complications.
In conclusion these mice will be used to investigate the mechanisms leading to development of secondary complications and they will also be used to design new therapies to abolish the serious long-term complications of diabetes mellitus.