Synergistic interactions of physiologic increments of glucagon, epinephrine, and cortisol in the dog: a model for stress-induced hyperglycemia.
Synergistic interactions of physiologic increments of glucagon, epinephrine, and cortisol in the dog: a model for stress-induced hyperglycemia.
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狗体内胰高血糖素、肾上腺素和皮质醇生理增量的协同相互作用：压力诱发的高血糖模型。
DOI：
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发表时间：
1979
影响因子：
15.9
通讯作者：
R. Sherwin
中科院分区：
文献类型：
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作者：
N. Eigler;L. Saccá;R. Sherwin
为了评估抗胰岛素激素的作用和相互作用在应激引起的高血糖发病机制中的作用，将反调节激素、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注入正常清醒的狗体内，剂量旨在模拟严重应激下观察到的变化。单独输注胰高血糖素、肾上腺素或皮质醇仅导致血浆葡萄糖浓度轻度或不显着升高。相比之下，任何两种反调节激素联合输注产生的血糖升高比各自单独输注的总和高出 50-215% (P < 0.005-0.001)。此外，当同时输注所有三种激素时，血浆葡萄糖浓度的增量（144+/-2 mg/dl）比单个激素输注的反应总和或双加单激素输注的任何组合的总和大两到四倍（P < 0.001）。单独输注胰高血糖素或肾上腺素会导致葡萄糖产量短暂增加（通过[3-(3)H]葡萄糖测量）。胰高血糖素输注伴随着葡萄糖清除率的上升，而肾上腺素则导致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，葡萄糖产量的增加是相加的，尽管是短暂的。然而，肾上腺素对葡萄糖清除的抑制作用占主导地位，从而解释了联合输注胰高血糖素和肾上腺素引起的过度血糖反应。虽然单独输注皮质醇对葡萄糖产生没有影响，但添加皮质醇显着加剧了胰高血糖素和（或）肾上腺素产生的高血糖，主要是通过维持这些激素产生的葡萄糖产生的增加。联合激素输注对β-羟基丁酸浓度没有影响。结论是：（a）正常狗中胰高血糖素、肾上腺素和皮质醇的生理增量相互作用，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产生的葡萄糖产生的升高； (c)这些数据表明，在几种反调节激素升高的情况下（例如“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。
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.