Adenovirus-mediated anti-apoptotic gene (bcl-2) transfer in the transplant pancreas

背景。高胰岛素血症通常与胰岛素抵抗有关，被认为是冠状动脉疾病的重要危险因素。本研究探讨胰腺移植后门静脉输送内源性胰岛素对血浆脂质代谢的影响，并与全身输送胰岛素进行比较。以正常大鼠为研究对象，采用门静脉与受体门静脉（PPTx）或下腔静脉（CPTx）吻合的方法，异位移植胰腺作为内源性高胰岛素血症的体内模型。CPTx和PPTx大鼠血浆胰岛素浓度均值分别为对照大鼠的149%和165%，而CPTx和PPTx大鼠血浆葡萄糖浓度与对照大鼠无显著差异。PPTx和CPTx大鼠血浆甘油三酯（TG）浓度均显著低于对照大鼠。静脉糖耐量试验时，CPTx和PPTx大鼠胰岛素浓度曲线下面积（AUC）分别为对照大鼠的204%和215%，与血浆TG浓度呈负相关。PPTx大鼠血浆胆固醇和TG浓度明显低于对照组和CPTx大鼠。慢性高胰岛素血症对胰腺移植大鼠血浆TG浓度的调节具有剂量依赖性抑制作用。PPTx大鼠的脂质水平明显低于CPTx大鼠，这表明与全身胰岛素递送相比，移植胰腺的胰岛素门静脉递送相对预防动脉粥样硬化过程。

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.