Gene therapy for type 1 diabetes. New approaches

Type 1 or insulin-dependent diabetes mellitus is a metabolic disease that results from the destruction of pancreatic beta-cells. Most patients receive subcutaneous insulin injections to reduce blood glucose levels. However, strict glucose control by multiple insulin injections is associated with an increased risk of hypoglycemia and weight gain, while a less strict glucose control is insufficient to prevent chronic complications such as nephropathy, neuropathy and retinopathy. Gene therapy holds a tremendous therapeutic potential to improve glycemic control by restoring endogenous insulin production. This review focuses on recent advances directed at producing insulin in an ectopic tissue as well as inducing pancreatic beta-cell neogenesis. The strategies include constitutive and promoter-regulated insulin expression in the liver; increasing hepatic glucose oxidation; insulin production from intestinal cells; and islet cell neogenesis in liver and pancreas.