Kim, Y D
(1Department of Internal Medicine &)
,
Park, K-G
(Institute for Medical Sciences, Keimyung University School of Medicine, Daegu, South Korea)
,
Morishita, R
(1Department of Internal Medicine &)
,
Kaneda, Y
(Institute for Medical Sciences, Keimyung University School of Medicine, Daegu, South Korea)
,
Kim, S-Y
(2Division of Gene Therapy Science, Osaka University Medical School, Osaka, Japan)
,
Song, D-K
(2Division of Gene Therapy Science, Osaka University Medical School, Osaka, Japan)
,
Kim, H-S
(3Department of Physiology, Keimyung University School of Medicine, Daegu, South Korea)
,
Nam, C-W
(3Department of Physiology, Keimyung University School of Medicine, Daegu, South Korea)
,
Lee, H C
(1Department of Internal Medicine &)
,
Lee, K-U
(Institute for Medical Sciences, Keimyung University School of Medicine, Daegu, South Korea)
,
Park, J-Y
(1Department of Internal Medicine &)
,
Kim, B-W
(Institute for Medical Sciences, Keimyung University School of Medicine, Daegu, South Korea)
,
Kim, J-G
(4Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea)
,
Lee, I-K
(5Department of Internal Medicine, Un)
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-ind...
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.Gene Therapy (2006) 13, 216–224. doi:10.1038/sj.gt.3302644; published online 22 September 2005
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.Gene Therapy (2006) 13, 216–224. doi:10.1038/sj.gt.3302644; published online 22 September 2005
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