Goldstein R E, Wasserman D H, McGuinness O P, Lacy D B, Cherrington A D, Abumrad N N
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Am J Physiol. 1993 Jan;264(1 Pt 1):E119-27. doi: 10.1152/ajpendo.1993.264.1.E119.
This study was undertaken to investigate the effects of chronic physiological elevations in plasma cortisol on glycogenolysis and gluconeogenesis in conscious, overnight-fasted dogs. Experiments consisted of an 80-min tracer and dye equilibration period and a 40-min sampling period. Infusions of D-[3-3H]glucose, L-[U-14C]alanine, and indocyanine green dye were used to assess glucose production (Ra) and gluconeogenesis using tracer and arteriovenous (a-v) difference techniques. In the cortisol group, (n = 10), a continuous infusion of hydrocortisone (3.5 micrograms.kg-1 x min-1) was begun 5 days before the experiment and continued throughout the sampling period. In the saline group (n = 10), there was no infusion of cortisol. The fivefold elevation in plasma cortisol increased plasma insulin from 12 +/- 2 to 19 +/- 2 microU/ml. Glucose Ra was elevated in the cortisol group (3.5 +/- 0.2 vs. 2.8 +/- 0.2 mg.kg-1 x min-1) but net hepatic glucose output was markedly diminished (1.2 +/- 0.4 vs. 2.7 +/- 0.3 mg.kg-1 x min-1). Gluconeogenic conversion of alanine to glucose was increased slightly by cortisol (0.60 +/- 0.13 to 0.99 +/- 0.12 mumol.kg-1 x min-1), but the gluconeogenic efficiency of the liver was unchanged. Cortisol increased hepatic glycogen content evident at the end of the study greater than twofold (76.4 +/- 7.9 vs. 30.0 +/- 4.7 g/liver). These results suggest that cortisol 1) promotes glucose cycling through glycogen, 2) greatly inhibits nonhepatic glucose utilization, 3) increases hepatic gluconeogenesis in vivo primarily through enhanced substrate delivery to the liver, and 4) raises plasma insulin levels, which restrains intrahepatic gluconeogenesis.
本研究旨在探讨血浆皮质醇慢性生理性升高对清醒、禁食过夜犬糖原分解和糖异生的影响。实验包括80分钟的示踪剂和染料平衡期以及40分钟的采样期。输注D-[3-³H]葡萄糖、L-[U-¹⁴C]丙氨酸和吲哚菁绿染料，采用示踪剂和动静脉（a-v）差值技术评估葡萄糖生成（Ra）和糖异生。在皮质醇组（n = 10）中，实验前5天开始持续输注氢化可的松（3.5微克·千克⁻¹·分钟⁻¹），并在整个采样期持续。在生理盐水组（n = 10）中，未输注皮质醇。血浆皮质醇升高五倍使血浆胰岛素从12±2微单位/毫升升高至19±2微单位/毫升。皮质醇组的葡萄糖Ra升高（3.5±0.2对2.8±0.2毫克·千克⁻¹·分钟⁻¹），但肝脏净葡萄糖输出明显减少（1.2±0.4对2.7±0.3毫克·千克⁻¹·分钟⁻¹）。皮质醇使丙氨酸向葡萄糖的糖异生转化略有增加（0.60±0.13至0.99±0.12微摩尔·千克⁻¹·分钟⁻¹），但肝脏的糖异生效率未改变。皮质醇使研究结束时肝脏糖原含量增加超过两倍（76.4±7.9对30.0±4.7克/肝脏）。这些结果表明，皮质醇1）促进葡萄糖通过糖原循环，2）极大地抑制非肝脏葡萄糖利用，3）主要通过增强底物向肝脏的输送增加体内肝脏糖异生，4）提高血浆胰岛素水平，从而抑制肝内糖异生。
