animal diabetes mellitus were controlled by a dietary treatment supplemented
with either a sulfonylurea drug or insulin injection. Insulin injections were
inconvenient and the hypoglycemia induced by insulin-overdose could be fatal.
Sulfonylurea drugs were administered orally, however, do not typically
provide satisfactory control of blood glucose as a starting treatment in 25% - 30%
patients. Therefore, it was imperative to develop a method for the control of human
and animal diabetes mellitus. Recently, insulin gene transferred and expressed
in non-pancreatic cells as a means for the treatment of diabetes was developed
rapidly in the expanding gene therapy. Retrovirus, lentivirus, adenovirus,
adenoassociated virus and herpes simplex had been used as viral vectors, and
the constructed viral-insulin gene was successfully transferred into diabetic
rat cells. A gene, containing promoter, enhancer and rat type I insulin gene
(a-chain, b-chain and signal peptide), was constructed into a retrovirus vector
in the study. The constructed viral-insulin gene was transferred into mouse
fibroblast cell. The insulin concentration in 3-day cultured mouse fibroblast cells
was 4806.35 ± 53.72 pg/ml. The insulin concentration for the viral vector
containing enhancer and promoter of rat insulin gene was higher than the
vector containing only insulin gene by a 61% increase in the cultured mouse
fibroblast cells. The enhancer and promoter activity of rat insulin gene would
be an important determinant for the expression of insulin gene. The secreted
amount of insulin by retrovirus vector contained enhancer/promoter gene in
this study could achieve as high concentrations (4806.35 ± 53.72 pg/ml) as the
insulin injection therapy. Blood glouse decreased sig-
nificantly for at last 10 days demonstratedthat transfection, direction injection of
viral-insulin gene into pancreas of diabetic rat, was successful. These studies
suggest that the retrovirus vector might be used to transfer the insulin gene
in vitro and in vivo.
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