Adenovirus-mediated insulin gene transfer improves nutritional and post-hepatectomized conditions in diabetic rats

Background. Impaired nutritional conditions in patients with diabetes are s ignificant risk factors after major abdominal surgery. We constructed recom binant adenovirus vector carrying the human insulin gene (AxCAIns) for in v ivo insulin gene transfer to improve metabolic impairments after a major op eration in patients with diabetes. We tested the effects of AxCAIns on nutr itional and post-hepatectomized conditions in rats with diabetes treated wi th streptozotocin (STZ) Methods. AxCAIns was injected into the spleen in diabetic rats treated with STZ. Blood levels of glucose, total protein, albumin, and C-peptide of hum an proinsulin were measured and the expression of transferred human insulin gene was analyzed in various organs. Diabetic rats underwent 70% partial h epatectomy with or without AxCAIns injection, and post-hepatectomized condi tions were analyzed. Results. STZ-induced hyperglycemia was reduced by AxCAIns injection. Decrea sed serum levels of total protein and albumin in diabetic rats were signifi cantly restored to normal levels by AsCAIns injection, and human C-peptide was detected in the sera of AxCAIns-treated rats. Human preproinsulin messe nger RNA, which represented the expression of transferred insulin gene, was detected in the liver and the spleen, but not in other organs. Serum album in levels, remnant liver weight, and ratios of postoperative body weight pr eoperative body weight were significantly increased by AxCAIns in hepatecto mized diabetic rants. Conclusions. AxCAIns injection to the spleen efficiently transferred the hu man insulin gene mainly into the hepatocytes and produced enough human proi nsulin to improve nutritional impairments and post-hepatectomized condition s in diabetic rats. Insulin gene transfer with intrasplenic injection of Ax CAIns may Be available to improve metabolic impairment after major abdomina l surgery in patients with diabetes.