Multiple genetic factors are involved in the pathogenesis of type 1 and type 2 diabetes mellitus. A defect, which
could be ascribed to a single or only few genes, has not been established yet. An exception represents the Maturity
Onset Diabetes of the Young (MODY) which is rather rare and is caused by mutations in some of 6 known genes.
Principles of gene therapy focus mainly on generation of replenishable sources of insulin producing tissue, which
could be used for replacement of the destroyed or failing β-cells. Current approaches include stimulation of embryonic
or adult stem cell proliferation and differentiation into β-cells, β-cell proliferation, transdifferentiation of non-islet
cells into glucose-sensitive insulin-producing cells and xenotransplantation. Genetic modification is being studied
to prevent islet rejection (e.g. local expression of immuno-suppressive cytokines or ligands inducing T-cell apoptosis,
knock-out of specific animal genes or transfer of human genes into animal tissue donors) or to construct „superislets“
resistant to apoptosis or oxidative stress. For prevention of type 1 diabetes and perhaps for induction of specific
immune tolerance vaccination with DNA fragments encoding for specific auto or alloantigens represents a promising
approach. In addition, gene therapy offers some hope for the future treatment of diabetic vascular complication,
neuropathy and syndromes of insulin resistance.
gene therapy, diabetes mellitus, transplantation, pancreatic islets, stem cells.