Insulin gene transfer with adenovirus vector via the spleen safely and effectively improves posthepatectomized conditions in diabetic rats.

Background: We examined administration methods of adenovirus vector carrying human insulin gene (AxCAIns), which could safely and effectively enhance liver regeneration in diabetic rats after hepatectomy.

Methods: Male Wistar rats were made diabetic with streptozotocin and subjected to 70% partial hepatectomy. AxCAIns was administrated into the spleen, the portal vein, the peritoneal cavity, or the femoral muscle. Liver regeneration and damage, and nutritional conditions were compared among the groups which were different in the administration methods of AxCAIns.

Results: Intrasplenic administration of AxCAIns enhanced liver regeneration, improving nutritional conditions without liver damage. In contrast, intraportal administration enhanced liver regeneration but caused hypoglycemia with liver damage. Neither intraperitoneal nor intramuscular administration produced detectable serum levels of human c-peptide, and did not enhance liver regeneration.

Conclusions: In conclusion, data showed that intrasplenic administration of AxCAIns, rather than other methods, effectively enhanced liver regeneration without liver damage and improved nutritional conditions after hepatectomy in diabetic rats. It is suggested that insulin gene transfer with AxCAIns via the spleen may safely and effectively improve posthepatectomized conditions in inslinopenic patients.