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Mol Ther. 2012 May;20(5):918-26. doi: 10.1038/mt.2012.8. Epub 2012 Feb 21.

Reversal of diabetes through gene therapy of diabetic rats by hepatic insulin expression via lentiviral transduction.

Author information

1
Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany.

Abstract

Due to shortage of donor tissue a cure for type 1 diabetes by pancreas organ or islet transplantation is an option only for very few patients. Gene therapy is an alternative approach to cure the disease. Insulin generation in non-endocrine cells through genetic engineering is a promising therapeutic concept to achieve insulin independence in patients with diabetes. In the present study furin-cleavable human insulin was expressed in the liver of autoimmune-diabetic IDDM rats (LEW.1AR1/Ztm-iddm) and streptozotocin-diabetic rats after portal vein injection of INS-lentivirus. Within 5-7 days after the virus injection of 7 × 10(9) INS-lentiviral particles the blood glucose concentrations were normalized in the treated animals. This glucose lowering effect remained stable for the 1 year observation period. Human C-peptide as a marker for hepatic release of human insulin was in the range of 50-100 pmol/ml serum. Immunofluorescence staining of liver tissue was positive for insulin showing no signs of transdifferentiation into pancreatic β-cells. This study shows that the diabetic state can be efficiently reversed by insulin release from non-endocrine cells through a somatic gene therapy approach.

PMID:
22354377
PMCID:
PMC3345991
DOI:
10.1038/mt.2012.8
[Indexed for MEDLINE]
Free PMC Article
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