Intravascular insulin gene delivery as potential therapeutic intervention in diabetes mellitus

被引：18

作者：

Yasutomi, K

Itokawa, Y

Asada, H

Kishida, T

Cui, FD

Ohashi, S

Gojo, S

Ueda, Y

Kubo, T

Yamagishi, H

Imanishi, J

Takeuchi, T

Mazda, O ^{[1
]}

机构：

[1] Kyoto Prefectural Univ Med, Dept Microbiol, Kyoto 6028566, Japan

[2] Kyoto Prefectural Univ Med, Dept Digest Surg, Kyoto 6028566, Japan

[3] Kyoto Prefectural Univ Med, Dept Orthopaed Surg, Kyoto 6028566, Japan

[4] Saitama Med Ctr, Dept Cardiovasc Surg, Kawagoe, Saitama 3508550, Japan

[5] Gunma Univ, Dept Mol Med, Inst Mol & Cellular Regulat, Gunma 3718512, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2003年 / 310卷 / 03期

关键词：

diabetes mellitus; insulin; naked DNA; Epstein-Barr virus; insulin gene promoter; gene therapy;

D O I：

10.1016/j.bbrc.2003.09.103

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

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. (C) 2003 Elsevier Inc. All rights reserved.

引用

页码：897 / 903

页数：7

共 36 条

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Insulin delivery with plasmid DNA [J].