| 摘 要： | AIM:Transfer and expression of insulin gene in vivo arean alternative strategy to improve glycemic control in type1 diabetes.Hydrodynamics-based procedure has beenproved to be very efficient to transfer naked DNA to mouselivers.The basal hepatic insulin production mediated bythis rapid tail vein injection was studied to determine itseffect on the resumption of glycemic control in type 1diabetic mice.METHODS:Engineered insulin cDNA was inserted intoplasmid vectors under a CMV promoter,and transferred intoSTZ induced diabetic mice by hydrodynamic procedure.Glucose levels,body weight of treated mice,insulin levels,immunohistology of the liver,and quantity of insulin mRNAin the liver were assayed to identify the improvement ofhyperglycemic complication after plasmid administration.Sleeping Beauty,a transposon system,was also used toprolong the insulin expression in the liver.RESULTS:After plasmid administration,Plasma insulin wassignificantly increased in the diabetic mice and the liverswere insulin-positive by immunostaining.At the same timethe hyperglycemic complication was improved,The bloodglucose levels of mice were reduced to normal.Glucosetolerance of the treated diabetic mice was improved,Bodyweight loss was also ameliorated.The rapid tail vein injectiondid not cause any fatal result.CONCLUSION:Our results suggested that insulin genecould be efficiently transferred into the livers of diabeticmice via rapid tail vein injection and it resulted in high levelof insulin expression.The basal hepatic insulin productionmediated by hydrodynamics-based administration improvedthe glycemic control in type 1 diabetes dramatically andameliorated diabetic syndromes.Hydrodynamics-basedadministration offers a simple and efficient way in the studyof gene therapy for type 1 diabetes.
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