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

FEBS Lett. 2001 Nov 30;509(1):106-10. doi: 10.1016/s0014-5793(01)03146-5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Adipose Tissue / metabolism*
  • Animals
  • Blotting, Southern
  • Diabetes Mellitus, Experimental / therapy*
  • Enzyme-Linked Immunosorbent Assay
  • Gene Transfer Techniques*
  • Glucose Tolerance Test
  • Hyperglycemia / therapy*
  • Immunoblotting
  • Immunohistochemistry
  • Insulin / blood
  • Mice
  • Mice, Obese
  • Models, Biological
  • Proinsulin / genetics*
  • Proinsulin / metabolism
  • Protein Precursors / genetics*
  • Protein Precursors / metabolism
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors


  • Insulin
  • Protein Precursors
  • RNA, Messenger
  • preproinsulin
  • Proinsulin