In vivo expression of rat insulin after intravenous administration of the liposome-entrapped gene for rat insulin I.
A recombinant plasmid encoding rat preproinsulin I was encapsulated in large liposomes and intravenously injected in rats. Glycemia and blood, splenic, and hepatic insulin were assayed at various times beginning 6 hr after inoculation. The results were compared with controls that had received (i) empty liposomes, (ii) liposomes carrying the Escherichia coli pBR322 plasmid, (iii) the free rat insulin I gene, and (iv) no injection at all. Whereas all controls showed unchanged glucose and insulin levels, the treated animals had, 6 hr after inoculation, a blood glucose level of 72 +/- 5 mg of glucose/100 ml of blood as compared with 107 +/- 2 mg/ml for controls. Radioimmunoassay of blood insulin gave 61 +/- 8 microunits/ml as compared with 43 +/- 5 microunits/ml for controls and the spleen and liver values were 242 +/- 22 and 204 +/- 20 microunits/g of tissue, respectively, as compared with 112 +/- 20 and 87 +/- 15 microunits/g in controls. External gamma-camera imaging of the organ uptake of 111In-labeled liposomes permitted study of the kinetics and extent of uptake of the liposomes by spleen and liver, results that support the findings concerning insulin synthesis in the two organs.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004274:DNA, Recombinant; D005786:Gene Expression Regulation; D007328:Insulin / Q000235:genetics*; D008081:Liposomes / Q000008:administration & dosage; D008099:Liver / Q000502:physiology; D051381:Rats; D013154:Spleen / Q000502:physiology; D013997:Time Factors; D014018:Tissue Distribution; D014170:Transformation, Genetic
D001786:Blood Glucose; D004274:DNA, Recombinant; D007328:Insulin; D008081:Liposomes