Non-viral adiponectin gene therapy into obese type 2 diabetic mice ameliorates insulin resistance.
Synthetic polymer vectors are attractive for gene delivery due to their potential safety and versatility. However, due to the low efficiency, most of the successful applications of polymeric vectors are focused on the therapeutic genes whose products have biological effects at low concentrations. Adiponectin is one of the abundant circulating proteins and possesses diverse effects including anti-hyperglycemic and anti-atherogenic properties. In this study, we performed the adiponectin gene delivery using a mini-circle DNA complexed with a polymeric carrier, polyethylenimine, into diet induced obese C57BL/6J mice. The mini-circle DNA showed much higher adiponectin expression than the conventional plasmid in vitro and in vivo. This strategy achieved a sufficient blood level of adiponectin and the parameters related with insulin resistance were normalized. The mini-circle DNA will be useful for the increased efficiency of polymeric vectors and adiponectin gene therapy which is applicable to the treatment of type 2 diabetes.
Park
Jeong Hyun
JH
Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, United States.
Lee
Minhyung
M
Kim
Sung Wan
SW
D055372:AMP-Activated Protein Kinases; D052242:Adiponectin / Q000097:blood / Q000235:genetics / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D004041:Dietary Fats / Q000009:adverse effects / Q000633:toxicity; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015870:Gene Expression / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009097:Multienzyme Complexes / Q000378:metabolism; D009765:Obesity / Q000139:chemically induced / Q000150:complications*; D010316:Particle Size; D010766:Phosphorylation; D010957:Plasmids / Q000737:chemistry / Q000235:genetics; D011094:Polyethyleneimine / Q000737:chemistry; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D014162:Transfection / Q000379:methods
D052242:Adiponectin; D001786:Blood Glucose; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D009097:Multienzyme Complexes; D011094:Polyethyleneimine; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases