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Liver-directed gene therapy of diabetic rats using an HVJ-E vector containing EBV plasmids expressing insulin and GLUT 2 transporter

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Author(s)
YD KimK-G ParkR MorishitaY KanedaS-Y KimD-K SongH-S KimC-W NamHC LeeK-U LeeJ-Y ParkB-W KimJ-G KimI-K Lee
Keimyung Author(s)
Park, Keun GyuKim, Hye SoonNam, Chang WookSong, Dae Kyu
Department
Dept. of Internal Medicine (내과학)
Dept. of Physiology (생리학)
Institute for Medical Science (의과학연구소)
Journal Title
Cancer Gene Therapy
Issued Date
2006
Volume
13
Issue
3
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 streptozotocininduced
diabetic rats with hemagglutinating virus of Japanenvelope
(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 glucosestimulated
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
Keywords: insulin; GLUT 2; HVJ-E; EBV; diabetes
Keimyung Author(s)(Kor)
박근규
김혜순
남창욱
송대규
Publisher
School of Medicine
Citation
YD Kim et al. (2006). Liver-directed gene therapy of diabetic rats using an
HVJ-E vector containing EBV plasmids expressing
insulin and GLUT 2 transporter. Cancer Gene Therapy, 13(3), 216–224. doi: 10.1038/sj.gt.3302644
Type
Article
ISSN
0969-7128
Source
http://www.nature.com/gt/journal/v13/n3/pdf/3302644a.pdf
DOI
10.1038/sj.gt.3302644
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35771
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
3. Research Institutues (연구소) > Institute for Medical Science (의과학연구소)
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