GENE-THERAPY FOR DIABETES-MELLITUS IN RATS BY HEPATIC EXPRESSION OF INSULIN

Type 1 diabetes mellitus is caused by severe insulin deficiency second ary to the autoimmune destruction of pancreatic beta cells. Patients n eed to be controlled by periodic insulin injections to prevent the dev elopment of ketoacidosis, which can be fatal. Sustained, low-level exp ression of the rat insulin 1 gene from the liver of severely diabetic rats was achieved by in vivo administration of a recombinant retrovira l vector. Ketoacidosis was prevented and the treated animals exhibited normoglycemia during a 24-hr fast, with no evidence of hypoglycemia. Histopathological examination of the liver in the treated animals show ed no apparent abnormalities. Thus, the liver is an excellent target o rgan for ectopic expression of the insulin gene as a potential treatme nt modality for type 1 diabetes mellitus by gene therapy.