Introduction and Expression of the Human Insulin Gene in Adult Rat Liver

Liposomes associated with gangliosides and loaded with the human insulin gene were incubated with HVJ (Sendai virus) and red blood cell membranes containing non-histone chromosomal protein, high mobility group 1 (HMG-1), or bovine serum albumin (BSA) to form vesicle complexes. These vesicle complexes were then injected into the portal vein of adult rats. The insulin gene co-introduced with HMG-1 was transported into the nuclei of liver cells much more efficiently than the gene co-introduced with BSA. Moreover, the amount of transcript of the insulin gene co-introduced with HMG-1 was more than 10 times greater than that of the gene co-introduced with BSA. Similar amounts of DNA and RNA of human insulin were found in the liver within 7 days after injection of the gene, and then the amounts of both decreased rapidly. The level of human insulin in rat serum gradually increased to a maximum (20-30 microunits/ml) after 7 or 8 days and then decreased rapidly.