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) em...

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Published in:Proceedings of the National Academy of Sciences - PNAS Vol. 80; no. 4; pp. 1068 - 1072
Main Authors: Nicolau, C, Le Pape, A, Soriano, P, Fargette, F, Juhel, M.F
Format: Journal Article
Language:English
Published: United States National Academy of Sciences of the United States of America 01-02-1983
National Acad Sciences
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Summary: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 γ -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.
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ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.80.4.1068