Adenovirus‐mediated preproinsulin gene transfer into adipose tissues ameliorates hyperglycemia in obese diabetic KKAy mice

FEBS Letters

Watanabe, Takashi²  Nagamatsu, Shinya³  Nakamichi, Yoko³  Ohara-Imaizumi, Mica³  Ozawa, Sachihiko¹  Ishida, Hitoshi¹  Katahira, Hitoshi¹ 

[1] Department of Internal Medicine (III), Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan;Department of Clinical Pathology, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan;Department of Biochemistry, Kyorin University School of Medicine, Shinkawa 6-20-2, Mitaka, Tokyo 181-8611, Japan

关键词: Adipocyte;    Gene therapy;    GLUT4;    Insulin;    Obesity;    Type 2 diabetes;    ELISA;    enzyme-linked immunosorbent assay;    FBS;    fetal bovine serum;    GLUT;    facilitated glucose transporter;    ipGTT;    intraperitoneal glucose tolerance test;    pchi;    human preproinsulin;    RT-PCR;    reverse transcriptase-polymerase chain reaction;   

DOI  :  10.1016/S0014-5793(01)03146-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We investigated whether adenovirus-mediated preproinsulin gene transfer into insulin target tissues (adipocytes) ameliorates hyperglycemia in diabetic mice. KKA^y mice, a genetically obese type 2 diabetic animal model, were treated with a single subcutaneous injection of recombinant adenovirus, Adex1CA-human preproinsulin (Adex1CA-pchi), into the epididymal fat pads. pchi mRNA was expressed only in adipose tissue in which mature insulin was produced. Three days after virus injection these mice showed a marked decrease of blood glucose levels (from about 400 to 200 mg/dl), and an intraperitoneal glucose tolerance test revealed the markedly improved glucose tolerance. There was no significant difference in serum insulin levels between control and recombinant adenovirus-treated KKA^y mice. The normalized glucose levels in diabetic mice were maintained for at least 2 weeks after the virus injection. This strategy could provide a novel and, most importantly, a simple and convenient gene therapy for obese type 2 diabetes patients.

【 授权许可】

Unknown