Adenovirus-mediated preproinsulin gene transfer into adipose tissues ameliorates hyperglycemia in obese diabetic KKA y mice

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, Adex...

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Bibliographic Details
Published in:FEBS letters 2001-11, Vol.509 (1), p.106-110
Main Authors: Nagamatsu, Shinya, Nakamichi, Yoko, Ohara-Imaizumi, Mica, Ozawa, Sachihiko, Katahira, Hitoshi, Watanabe, Takashi, Ishida, Hitoshi
Format: Article
Language:English
Subjects:
Adipocyte
Gene therapy
GLUT4
Insulin
Obesity
Type 2 diabetes
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Summary: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.
ISSN:0014-5793
1873-3468
DOI:10.1016/S0014-5793(01)03146-5