Fujiwara T, Cherrington A D, Neal D N, McGuinness O P
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232-0615, USA.
Metabolism. 1996 May;45(5):571-8. doi: 10.1016/s0026-0495(96)90026-8.
The role of cortisol in directing the metabolic response to a combined infusion of glucagon, epinephrine, norepinephrine, and cortisol (stress hormones) was investigated. Chronically catheterized, conscious fasted dogs were studied before hormone infusion and after a 70-hour stress hormone infusion containing glucagon, epinephrine, norepinephrine, and cortisol (n = 11) or containing all these hormones except cortisol (n = 5). Combined stress hormone infusion increased arterial plasma glucagon, cortisol, epinephrine, and norepinephrine approximately sixfold. Whole-body glucose production (Ra), glycogenolysis, and gluconeogenesis were assessed using tracer and arteriovenous-difference techniques. The absence of an increase in cortisol during stress hormone infusion attenuated the increase in arterial plasma glucose concentration and Ra (delta 81 +/- 16 v 24 +/- 3 mg/dL and 1.7 +/- 0.3 v 0.8 +/- 0.4 mg/ kg/min, respectively). However, it did not alter the increase in net hepatic glucose output (delta 0.7 +/- 0.3 v 0.8 +/- 0.4 mg/kg/min). When the increase in cortisol was absent, the increase in net hepatic gluconeogenic precursor uptake was attenuated (delta 0.7 +/- 0.3 v 0.1 +/- 0.3 mg glucose/kg/min) due to a decrease in gluconeogenic precursor levels. The efficiency of gluconeogenesis increased to a greater extent (delta 0.19 +/- 0.07 v 0.31 +/- 0.11) when cortisol was not infused. The absence of an increase in cortisol also led to marked glycogen depletion in the liver (10 +/- 4 v 55 +/- 10 mg/g liver). Cortisol thus plays a pivotal role in the metabolic response to stress hormone infusion by sustaining gluconeogenesis through a stimulatory effect on hepatic gluconeogenic precursor supply and by maintaining hepatic glycogen availability.
研究了皮质醇在指导对胰高血糖素、肾上腺素、去甲肾上腺素和皮质醇（应激激素）联合输注的代谢反应中的作用。对长期插管的清醒禁食犬在激素输注前以及在输注含胰高血糖素、肾上腺素、去甲肾上腺素和皮质醇的应激激素70小时后（n = 11）或输注除皮质醇外的所有这些激素后（n = 5）进行了研究。联合应激激素输注使动脉血浆胰高血糖素、皮质醇、肾上腺素和去甲肾上腺素增加了约六倍。使用示踪剂和动静脉差技术评估全身葡萄糖生成（Ra）、糖原分解和糖异生。在应激激素输注期间皮质醇未增加，减弱了动脉血浆葡萄糖浓度和Ra的增加（分别为δ81±16对24±3mg/dL和1.7±0.3对0.8±0.4mg/kg/min）。然而，它并未改变肝脏净葡萄糖输出的增加（δ0.7±0.3对0.8±0.4mg/kg/min）。当皮质醇未增加时，由于糖异生前体水平降低，肝脏净糖异生前体摄取的增加减弱（δ0.7±0.3对0.1±0.3mg葡萄糖/kg/min）。当不输注皮质醇时，糖异生效率增加的程度更大（δ0.19±0.07对0.31±0.11）。皮质醇未增加还导致肝脏中糖原显著耗竭（10±4对55±10mg/g肝脏）。因此，皮质醇在对应激激素输注的代谢反应中起关键作用，通过对肝脏糖异生前体供应的刺激作用维持糖异生，并维持肝脏糖原的可用性。
