Abstract
Insulin gene therapy in clinical medicine is currently hampered by the inability to regulate insulin secretion in a physiological manner, the inefficiency with which the gene is delivered, and the short duration of gene expression. To address these issues, we injected the liver of streptozotocin-induced diabetic rats with hemagglutinating virus of Japan-envelope (HVJ-E) vectors containing Epstein -Barr virus (EBV) plasmids encoding the genes for insulin and the GLUT 2 transporter. Efficient delivery of the genes was achieved with the HVJ-E vector, and the use of the EBV replicon vector led to prolonged hepatic gene expression. Blood glucose levels were normalized for at least 3 weeks as a result of the gene therapy. Cotransfection of GLUT 2 with insulin permitted the diabetic rats to regulate their blood glucose levels upon exogenous glucose loading in a physiologically appropriate manner and improved postprandial glucose levels. Moreover, cotransfection with insulin and GLUT 2 genes led to in vitro glucose-stimulated insulin secretion that involved the closure of KATP channels. The present study represents a new way to efficiently deliver insulin gene in vivo that is regulated by ambient glucose level with prolonged gene expression. This may provide a basis to overcome limitations of insulin gene therapy in humans.
Original language | English |
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Pages (from-to) | 216-224 |
Number of pages | 9 |
Journal | Gene Therapy |
Volume | 13 |
Issue number | 3 |
DOIs | |
State | Published - Feb 2006 |
Keywords
- Diabetes
- EBV
- GLUT 2
- HVJ-E
- Insulin