Gene therapy for diabetes mellitus in rats by hepatic expression of insulin.
Type 1 diabetes mellitus is caused by severe insulin deficiency secondary to the autoimmune destruction of pancreatic beta cells. Patients need to be controlled by periodic insulin injections to prevent the development of ketoacidosis, which can be fatal. Sustained, low-level expression of the rat insulin 1 gene from the liver of severely diabetic rats was achieved by in vivo administration of a recombinant retroviral 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 showed no apparent abnormalities. Thus, the liver is an excellent target organ for ectopic expression of the insulin gene as a potential treatment modality for type 1 diabetes mellitus by gene therapy.
Kolodka
T M
TM
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA.
Finegold
M
M
Moss
L
L
Woo
S L
SL
D000818:Animals; D001483:Base Sequence; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000628:therapy*; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D005934:Glucagon / Q000097:blood; D007328:Insulin / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D007659:Ketones / Q000097:blood; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D011994:Recombinant Proteins / Q000627:therapeutic use; D012190:Retroviridae / Q000235:genetics; D013311:Streptozocin; D016019:Survival Analysis; D014161:Transduction, Genetic
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D007659:Ketones; D011994:Recombinant Proteins; D013311:Streptozocin; D005934:Glucagon