Intravascular insulin gene delivery as potential therapeutic intervention in diabetes mellitus.
We assessed therapeutic potential of intravascular insulin gene delivery in a diabetic murine model. The rat proinsulin-1 gene cDNA engineered to harbor furin consensus cleavage sequences was inserted into EBV-based plasmid vectors that contained CAG promoter or multimerized rat insulin promoter (RIP). Normal or streptozotocin (STZ)-induced diabetic mice were given an injection of the plasmids via the tail vein under high pressure. Transfection of the CAG-proinsulin construct markedly improved hyperglycemia of diabetic mice, accompanied by a considerable increase in serum insulin concentrations. Although the RIP-plasmid failed to reduce fasting blood glucose, the glucose tolerance test and RT-PCR analysis revealed that insulin production was regulated in the liver in a blood glucose level-dependent manner. The present results suggest a potential therapeutic means of controlling DM.
Yasutomi
Kakei
K
Department of Microbiology, Kyoto Prefectural University of Medicine, Japan.
Itokawa
Yoshiki
Y
Asada
Hidetsugu
H
Kishida
Tsunao
T
Cui
Feng-De
FD
Ohashi
Suzuyo
S
Gojo
Satoshi
S
Ueda
Yuji
Y
Kubo
Toshikazu
T
Yamagishi
Hisakazu
H
Imanishi
Jiro
J
Takeuchi
Toshiyuki
T
Mazda
Osam
O
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D007328:Insulin / Q000235:genetics*; D051379:Mice; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection
D001786:Blood Glucose; D018076:DNA, Complementary; D007328:Insulin; D005947:Glucose