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, 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.
Nagamatsu
S
S
Department of Biochemistry, Kyorin University School of Medicine, Tokyo, Japan. shinya@kyorin-u.ac.jp
Nakamichi
Y
Y
Ohara-Imaizumi
M
M
Ozawa
S
S
Katahira
H
H
Watanabe
T
T
Ishida
H
H
D000256:Adenoviridae / Q000235:genetics*; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D015139:Blotting, Southern; D003921:Diabetes Mellitus, Experimental / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D018014:Gene Transfer Techniques; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000628:therapy*; D015151:Immunoblotting; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D051379:Mice; D008820:Mice, Obese; D008954:Models, Biological; D011384:Proinsulin / Q000235:genetics* / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D007328:Insulin; D011498:Protein Precursors; D012333:RNA, Messenger; C013737:preproinsulin; D011384:Proinsulin