Adenovirus-mediated anti-apoptotic gene (bcl-2) transfer in the transplant pancreas
Grant-in-Aid for Scientific Research (C)
|Allocation Type||Single-year Grants|
|Research Institution||Tokyo University|
MAKUUCHI Masatoshi(1999) University of Tokyo, Faculty of Medicine, Professor, 医学部・附属病院, 教授 (60114641)
青柳 信嘉 東大, 医学部附属病院, 助手 (90292903)
SHIONOIRI Futoshi University of Tokyo, Faculty of Medicine, Assistant, 医学部・附属病院, 医員
MIURA Yasuaki University of Tokyo, Faculty of Medicine, Assistant, 医学部・附属病院, 医員
ABE Hideki University of Tokyo, Faculty of Medicine, Assistant, 医学部・附属病院, 医員
ISHIBASHI Shun University of Tokyo, Faculty of Medicine, Assistant Prof., 医学部・附属病院, 助手 (90212919)
HARADA Kenji University of Tokyo, Faculty of Medicine, Assistant, 医学部・附属病院, 医員
山田 信博 東京大学, 医学部・附属病院, 助教授 (40200729)
幕内 雅敏 東京大学, 医学部・附属病院, 教授 (60114641)
|Project Period (FY)
1998 – 1999
Completed(Fiscal Year 1999)
|Budget Amount *help
¥3,300,000 (Direct Cost : ¥3,300,000)
Fiscal Year 1999 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1998 : ¥2,600,000 (Direct Cost : ¥2,600,000)
|Keywords||pancreas / transplantation / insulin / adenovirus / Bcl2 (anti-apoptotic gene) / アデノウィルス / Bcl_2 / 拒絶反応 / 膵臓移植|
Background. Hyperinsulinemia, which is usually related to insulin resistance, is considered to be an important risk factor for coronary artery disease. The present study examines the influence of portal delivery of endogenous insulin after pancreas transplantation on plasma lipid metabolism, as compared to systemic delivery of insulin.
Method. Pancreas was transplanted heterotopically in normal rats by anastomosis of the donor portal vein to the recipient portal vein (PPTx) or inferior vena cava (CPTx) as an in vivo model of endogenous hyperinsulinemia.
Results. The mean value of plasma insulin concentration of CPTx and PPTx rats was 149% and 165% that of control rats, whereas the plasma glucose concentration of CPTx and PPTx rats did not differ significantly from that of control rats. Plasma triglyceride (TG) concentrations were significantly lower in both PPTx and CPTx rats than control rats. During the intravenous glucose tolerance test, the area under the insulin concentration curves (AUC) of CPTx and PPTx rats was 204% and 215% that of control rats, and they were correlated negatively with plasma TG concentrations. Plasma cholesterol and TG concentrations were significantly lower in PPTx rats than in control and CPTx rats.
Conclusions. Chronic hyperinsulinemia has a dose-dependent inhibitory effect on the regulation of plasma TG concentrations in rats with a transplanted pancreas. Significant lower lipid levels in PPTx rats than in CPTx rats suggest that portal delivery of insulin from the transplanted pancreas is relatively preventive for the atherosclerotic process as compared to systemic delivery of insulin.
Research Output (6results)