Goldstein R E, Reed G W, Wasserman D H, Williams P E, Lacy D B, Buckspan R, Abumrad N N, Cherrington A D
Department of Molecular Physiology and Biophysics, Surgery, Vanderbilt University School of Medicine, Nashville, TN 37232.
Metabolism. 1992 Dec;41(12):1295-303. doi: 10.1016/0026-0495(92)90099-v.
The present study was undertaken to determine whether an acute physiological increase in plasma cortisol level had significant effects on alanine metabolism and gluconeogenesis within 3 hours in conscious, overnight-fasted dogs. Each experiment consisted of an 80-minute tracer and dye equilibration period, a 40-minute basal period, and a 3-hour experimental period. A primed, continuous infusion of [3-3H]glucose and continuous infusions of [U-14C]alanine and indocyanine green dye were initiated at the start of the equilibration period and continued throughout the experiment. Dogs were studied with (1) a hydrocortisone infusion ([CORT] 3.0 micrograms.kg-1.min-1, n = 5), (2) hydrocortisone infused as in CORT, but with pancreatic hormones clamped using somatostatin and basal intraportal replacement of insulin and glucagon (CLAMP+CORT, n = 5), or (3) saline infusion during a pancreatic clamp (CLAMP, n = 5). Glucose production and gluconeogenesis were determined using tracer and arteriovenous difference techniques. During CLAMP, all parameters were stable except for a modest 67% +/- 6% increase in gluconeogenic conversion of alanine to glucose and a 53% +/- 26% increase in gluconeogenic efficiency. When plasma cortisol levels were increased fourfold during CLAMP+CORT, there was no change in the concentration, production, or clearance of glucose. Gluconeogenic conversion of alanine to glucose increased 10% +/- 34% and gluconeogenic efficiency increased 65% +/- 43%, while net hepatic alanine uptake (NHAU) increased 60% +/- 19% and hepatic fractional extraction of alanine increased 38% +/- 12%. Cortisol did not cause an increase in the arterial glycerol level or net hepatic glycerol uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究旨在确定清醒、禁食过夜的犬类在3小时内血浆皮质醇水平的急性生理升高是否对丙氨酸代谢和糖异生有显著影响。每个实验包括一个80分钟的示踪剂和染料平衡期、一个40分钟的基础期以及一个3小时的实验期。在平衡期开始时启动[3-3H]葡萄糖的预充连续输注以及[U-14C]丙氨酸和吲哚菁绿染料的连续输注，并在整个实验过程中持续。对犬类进行如下研究：（1）氢化可的松输注（[皮质醇]3.0微克·千克-1·分钟-1，n = 5）；（2）如在皮质醇组中那样输注氢化可的松，但使用生长抑素钳制胰腺激素，并通过门静脉内基础替代胰岛素和胰高血糖素（钳制+皮质醇组，n = 5）；或（3）在胰腺钳制期间输注生理盐水（钳制组，n = 5）。使用示踪剂和动静脉差值技术测定葡萄糖生成和糖异生。在钳制组期间，除了丙氨酸向葡萄糖的糖异生转化率适度增加67%±6%以及糖异生效率增加53%±26%外，所有参数均稳定。当在钳制+皮质醇组期间血浆皮质醇水平增加四倍时，葡萄糖的浓度、生成或清除率没有变化。丙氨酸向葡萄糖的糖异生转化率增加10%±34%，糖异生效率增加65%±43%，而肝脏丙氨酸净摄取量（NHAU）增加60%±19%，肝脏丙氨酸分数提取率增加38%±12%。皮质醇并未导致动脉甘油水平或肝脏甘油净摄取量增加。（摘要截取自250字）
