In vivo expression of rat insulin after intravenous administration of the liposome-entrapped gene for rat insulin I.

Abstract

A recombinant plasmid encoding rat preproinsulin I was encapsulated in large liposomes and i.v. injected in rats. Glycemia and blood, splenic, and hepatic insulin were assayed at various times beginning 6 h after inoculation. The results were compared with controls that had received empty liposomes, liposomes carrying the Escherichia coli pBR322 plasmid, the free rat insulin I gene, and no injection at all. Whereas all controls showed unchanged glucose and insulin levels, the treated animals had, 6 h 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 .mu.U/ml as compared with 43 .+-. 5 .mu.U/ml for controls and the spleen and liver values were 242 .+-. 22 and 204 .+-. 20 .mu.U/g of tissue, respectively, as compared with 112 .+-. 20 and 87 .+-. 15 .mu.U/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 2 organs.