Chap Z, Ishida T, Chou J, Michael L, Hartley C, Entman M, Field J B
J Clin Invest. 1986 Apr;77(4):1357-69. doi: 10.1172/JCI112441.
In conscious dogs, phentolamine infusion significantly increased fasting portal vein insulin, glucagon, and decreased net hepatic glucose output and plasma glucose. Propranolol significantly decreased portal vein insulin, portal flow, and increased hepatic glucose production and plasma glucose. Phentolamine, propranolol, and combined blockade reduced glucose absorption after oral glucose. alpha, beta, and combined blockade abolished the augmented fractional hepatic insulin extraction after oral glucose. Despite different absolute amounts of glucose absorbed and different amounts of insulin reaching the liver, the percent of the absorbed glucose retained by the liver was similar for control and with alpha- or beta blockade, but markedly decreased with combined blockade. Our conclusions are: (a) phentolamine and propranolol effects on basal hepatic glucose production may predominantly reflect their action on insulin and glucagon secretion; (b) after oral glucose, alpha- and beta-blockers separately or combined decrease glucose release into the portal system; (c) net hepatic glucose uptake is predominantly determined by hyperglycemia but can be modulated by insulin and glucagon; (d) direct correlation does not exist between hepatic delivery and uptake of insulin and net hepatic glucose uptake; (e) alterations in oral glucose tolerance due to adrenergic blockers, beyond their effects on glucose absorption, can be, to a large extent, mediated by their effects on insulin and glucagon secretion reflecting both hepatic and peripheral glucose metabolism.
在清醒犬中，静脉输注酚妥拉明可显著增加空腹门静脉胰岛素、胰高血糖素水平，并降低肝脏葡萄糖净输出量和血糖水平。普萘洛尔可显著降低门静脉胰岛素水平、门静脉血流量，并增加肝脏葡萄糖生成量和血糖水平。酚妥拉明、普萘洛尔及联合阻断可降低口服葡萄糖后的葡萄糖吸收。α、β及联合阻断可消除口服葡萄糖后肝脏胰岛素摄取分数的增加。尽管葡萄糖吸收的绝对量不同，到达肝脏的胰岛素量也不同，但对照组以及α或β阻断组肝脏保留的吸收葡萄糖百分比相似，而联合阻断时则显著降低。我们的结论是：(a) 酚妥拉明和普萘洛尔对基础肝脏葡萄糖生成的影响可能主要反映了它们对胰岛素和胰高血糖素分泌的作用；(b) 口服葡萄糖后，α和β受体阻滞剂单独或联合使用均可减少葡萄糖释放至门静脉系统；(c) 肝脏葡萄糖净摄取主要由高血糖决定，但可受胰岛素和胰高血糖素调节；(d) 肝脏胰岛素的输送和摄取与肝脏葡萄糖净摄取之间不存在直接相关性；(e) 肾上腺素能阻滞剂引起的口服葡萄糖耐量改变，除了对葡萄糖吸收的影响外，在很大程度上可由其对胰岛素和胰高血糖素分泌的影响介导，这反映了肝脏和外周的葡萄糖代谢。
