Baylor P, Shilo S, Zonszein J, Shamoon H
Am J Physiol. 1986 Sep;251(3 Pt 1):E322-7. doi: 10.1152/ajpendo.1986.251.3.E322.
Spontaneous or propranolol-induced hypoglycemia can occur in uremic humans. We studied glucose kinetics (using [3-3H]glucose) in five uremic humans 24 h after hemodialysis and in seven normal controls. The effect of glucagon infusion at rates of 3, 6, 12, and 18 ng X kg-1 X min-1 at 60-min intervals was compared with either saline or beta-adrenergic blockade (propranolol infusion). In uremics, plasma glucose increased by 20-25% and by 40-50% at the 3 and 6 ng X kg-1 X min-1 glucagon doses, respectively, with no further increases at higher infusion rates. Glucose production increased transiently and in tandem with glucose uptake at each glucagon increment (P less than 0.0001). During beta-adrenergic blockade, the effect of glucagon in stimulating glucose production was blunted by 14-24% at the 6-18 ng X kg-1 X min-1 doses (P less than 0.05). During saline infusion, plasma insulin concentrations increased progressively to peak levels fourfold above basal at the 18 ng X kg-1 X min-1 dose. This increase in plasma insulin was virtually abolished by concomitant beta-adrenergic blockade (P = 0.0002). In contrast to uremic subjects, normal controls exhibited lesser degrees of hyperglycemia and hyperinsulinemia at all glucagon infusion rates. Propranolol infusion had no effect on the increments in glucose production and uptake nor on the plasma insulin response. These results suggest that in uremic humans propranolol independently reduces the hepatic response to glucagon and the insulin secretory response to hyperglycemia and/or hyperglucagonemia. These observations provide a possible mechanism for the adrenergic regulation of glucose homeostasis in uremia.
自发性或普萘洛尔诱发的低血糖可发生于尿毒症患者。我们在5例尿毒症患者血液透析24小时后以及7名正常对照者中研究了葡萄糖动力学（使用[3-³H]葡萄糖）。以3、6、12和18 ng·kg⁻¹·min⁻¹的速率每隔60分钟输注胰高血糖素，将其效果与输注生理盐水或β-肾上腺素能阻滞剂（普萘洛尔输注）进行比较。在尿毒症患者中，分别给予3和6 ng·kg⁻¹·min⁻¹剂量的胰高血糖素时，血浆葡萄糖分别升高20% - 25%和40% - 50%，更高输注速率时无进一步升高。每次增加胰高血糖素时，葡萄糖生成短暂增加并与葡萄糖摄取同步增加（P < 0.0001）。在β-肾上腺素能阻滞期间，6 - 18 ng·kg⁻¹·min⁻¹剂量的胰高血糖素刺激葡萄糖生成的作用减弱14% - 24%（P < 0.05）。在输注生理盐水期间，血浆胰岛素浓度逐渐升高，在18 ng·kg⁻¹·min⁻¹剂量时达到基础水平的四倍峰值。同时进行β-肾上腺素能阻滞时，这种血浆胰岛素的升高几乎完全被消除（P = 0.0002）。与尿毒症患者相反，正常对照者在所有胰高血糖素输注速率下的高血糖和高胰岛素血症程度较轻。输注普萘洛尔对葡萄糖生成和摄取的增加以及血浆胰岛素反应均无影响。这些结果表明，在尿毒症患者中，普萘洛尔独立降低肝脏对胰高血糖素的反应以及胰岛素对高血糖和/或高胰高血糖素血症的分泌反应。这些观察结果为尿毒症中肾上腺素能调节葡萄糖稳态提供了一种可能的机制。
