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.
Department of Medical and Molecular Genetics and Center for Diabetes Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA. nmorralc@iupui.edu
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D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000235:genetics* / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D007515:Islets of Langerhans / Q000502:physiology; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008099:Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology; D045664:Proprotein Convertase 1 / Q000235:genetics; D045706:Proprotein Convertase 2 / Q000235:genetics; D012038:Regeneration
D007328:Insulin; D005941:Glucokinase; D045664:Proprotein Convertase 1; D045706:Proprotein Convertase 2; D005947:Glucose