Eigler N, Saccà L, Sherwin R S
J Clin Invest. 1979 Jan;63(1):114-23. doi: 10.1172/JCI109264.
To evaluate the role of anti-insulin hormone actions and interactions in the pathogenesis of stress-induced hyperglycemia, the counterregulatory hormones, glucagon, epinephrine, and cortisol were infused alone as well as in double and triple combinations into normal conscious dogs in doses that were designed to simulate changes observed in severe stress. Infusion of glucagon, epinephrine, or cortisol alone produced only mild or insignificant elevations in plasma glucose concentration. In contrast, the rise in plasma glucose produced by combined infusion of any two counterregulatory hormones was 50-215% greater (P < 0.005-0.001) than the sum of the respective individual infusions. Furthermore, when all three hormones were infused simultaneously, the increment in plasma glucose concentration (144+/-2 mg/dl) was two- to fourfold greater than the sum of the responses to the individual hormone infusions or the sum of any combination of double plus single hormone infusion (P < 0.001). Infusion of glucagon or epinephrine alone resulted in a transient rise in glucose production (as measured by [3-(3)H]glucose). While glucagon infusion was accompanied by a rise in glucose clearance, with epinephrine there was a sustained, 20% fall in glucose clearance. When epinephrine was infused together with glucagon, the rise in glucose production was additive, albeit transient. However, the inhibitory effect of epinephrine on glucose clearance predominated, thereby accounting for the exaggerated glycemic response to combined infusion of glucagon and epinephrine. Although infusion of cortisol alone had no effect on glucose production, the addition of cortisol markedly accentuated hyperglycemia produced by glucagon and(or) epinephrine primarily by sustaining the increases in glucose production produced by these hormones. The combined hormonal infusions had no effect on beta-hydroxybutyrate concentration. It is concluded that (a) physiologic increments in glucagon, epinephrine, and cortisol interact synergistically in the normal dog so as to rapidly produce marked fasting hyperglycemia; (b) in this interaction, epinephrine enhances glucagon-stimulated glucose output and interferes with glucose uptake while cortisol sustains elevations in glucose production produced by epinephrine and glucagon; and (c) these data indicate that changes in glucose metabolism in circumstances in which several counterregulatory hormones are elevated (e.g., "stress hyperglycemia") are a consequence of synergistic interactions among these hormones.
为评估抗胰岛素激素的作用及相互作用在应激性高血糖发病机制中的作用，将升糖调节激素胰高血糖素、肾上腺素和皮质醇单独以及以双重和三重组合的形式，以旨在模拟严重应激时所观察到变化的剂量，输注到正常清醒犬体内。单独输注胰高血糖素、肾上腺素或皮质醇仅使血浆葡萄糖浓度出现轻度升高或无显著升高。相比之下，任何两种升糖调节激素联合输注所引起的血浆葡萄糖升高幅度比各自单独输注之和高50% - 215%（P < 0.005 - 0.001）。此外，当同时输注所有三种激素时，血浆葡萄糖浓度的升高幅度（144±2mg/dl）比单独激素输注反应之和或任何双重加单一激素输注组合反应之和高两到四倍（P < 0.001）。单独输注胰高血糖素或肾上腺素会导致葡萄糖生成短暂增加（通过[3-(3)H]葡萄糖测量）。输注胰高血糖素时伴有葡萄糖清除率升高，而输注肾上腺素时葡萄糖清除率持续下降20%。当肾上腺素与胰高血糖素一起输注时，葡萄糖生成的增加具有相加性，尽管是短暂的。然而，肾上腺素对葡萄糖清除率的抑制作用占主导，从而解释了对胰高血糖素和肾上腺素联合输注的血糖反应过度增强的原因。尽管单独输注皮质醇对葡萄糖生成没有影响，但加入皮质醇会显著加重胰高血糖素和（或）肾上腺素所引起的高血糖，主要是通过维持这些激素所产生的葡萄糖生成增加。联合激素输注对β-羟丁酸浓度没有影响。得出以下结论：（a）在正常犬中，胰高血糖素、肾上腺素和皮质醇的生理性增加相互协同作用，从而迅速产生明显的空腹高血糖；（b）在这种相互作用中，肾上腺素增强胰高血糖素刺激的葡萄糖输出并干扰葡萄糖摄取，而皮质醇维持肾上腺素和胰高血糖素所产生的葡萄糖生成增加；（c）这些数据表明，在几种升糖调节激素升高的情况下（如“应激性高血糖”），葡萄糖代谢的变化是这些激素之间协同相互作用的结果。
