Shamoon H, Hendler R, Sherwin R S
J Clin Endocrinol Metab. 1981 Jun;52(6):1235-41. doi: 10.1210/jcem-52-6-1235.
We infused epinephrine, glucagon, and cortisol in combination into health overnight-fasted subjects in doses designed to simulate changes in severe stress. When all three hormones were infused simultaneously, glucose levels rose above 200 mg/dl in spite of a 100-200% increase in plasma insulin. In contrast, infusion of each hormone individually produced either a mild (less than 120 mg/dl) or a transient elevation in the plasma glucose concentration. With the combined hormone infusion, the increment in plasma glucose was 3-fold greater than the sum of the responses to the individual hormones (P less than 0.001). The marked hyperglycemia in this setting is a result of ongoing glucose overproduction which is stimulated by epinephrine and glucagon and sustained by cortisol. Furthermore, epinephrine (and possibly cortisol) inhibited glucose disposal despite concomitant hyperinsulinemia. In contrast to their effects on glucose regulation, the simultaneous infusion of epinephrine, glucagon, and cortisol failed to cause hyperketonemia. We conclude that the combined infusion of epinephrine, glucagon, and cortisol produces a greater than additive hyperglycemic response in normal humans. These data suggest that the clinical occurrence of fasting hyperglycemia in a setting of hypersecretion of multiple antiinsulin hormones (stress hyperglycemia) may result, at least in part, from synergistic interactions among these hormones.
我们将肾上腺素、胰高血糖素和皮质醇联合输注给夜间禁食的健康受试者，输注剂量旨在模拟严重应激时的变化。当同时输注这三种激素时，尽管血浆胰岛素增加了100 - 200%，血糖水平仍升至200mg/dl以上。相比之下，单独输注每种激素只会使血浆葡萄糖浓度出现轻度升高（低于120mg/dl）或短暂升高。联合输注激素时，血浆葡萄糖的增量比单独输注激素时的反应总和大3倍（P < 0.001）。这种情况下明显的高血糖是由于肾上腺素和胰高血糖素刺激持续的葡萄糖过度生成，并由皮质醇维持。此外，尽管同时存在高胰岛素血症，肾上腺素（可能还有皮质醇）仍抑制葡萄糖的利用。与它们对葡萄糖调节的作用相反，同时输注肾上腺素、胰高血糖素和皮质醇并未导致酮血症。我们得出结论，联合输注肾上腺素、胰高血糖素和皮质醇在正常人体内产生的高血糖反应大于各激素单独作用之和。这些数据表明，在多种抗胰岛素激素分泌过多的情况下（应激性高血糖），空腹高血糖的临床发生可能至少部分源于这些激素之间的协同相互作用。
