Goldstein R E, Cherrington A D, Reed G W, Lacy D B, Wasserman D H, Abumrad N N
Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee.
Am J Physiol. 1994 Apr;266(4 Pt 1):E618-27. doi: 10.1152/ajpendo.1994.266.4.E618.
This study was undertaken to further investigate the effect of acute selective insulin deficiency on glycogenolysis and gluconeogenesis occurring during chronic physiological hypercortisolemia in conscious overnight fasted dogs. After an 80-min tracer and dye equilibration period and a 40-min basal period, selective insulin deficiency was created during the 180-min experimental period by infusing somatostatin peripherally (0.8 micrograms.kg-1.min-1) with basal replacement of glucagon intraportally (0.65 ng.kg-1.min-1). In the cortisol group (n = 5), a continuous infusion of hydrocortisone (3.5 micrograms.kg-1.min-1) was begun 5 days before the experiment. In the saline group (n = 5), there was no infusion of cortisol. [3-3H]glucose, [U-14C]alanine, and indocyanine green dye were used to assess glucose production and gluconeogenesis using tracer and arteriovenous difference techniques. During selective insulin deficiency in the saline group, the arterial plasma glucose level (Glc) increased from 109 +/- 2 to 285 +/- 19 mg/dl; glucose production increased from 2.7 +/- 0.2 to 4.5 +/- 0.3 mg.kg-1.min-1. Gluconeogenic efficiency and conversion of alanine to glucose (Conv) increased by 300 +/- 55 and 356 +/- 67%. During selective insulin deficiency in the cortisol group, Glc increased from 117 +/- 3 to 373 +/- 50 mg/dl; glucose production increased from 3.3 +/- 0.5 to 6.9 +/- 0.7 mg.kg-1.min-1. Gluconeogenic efficiency and Conv increased by 268 +/- 41 and 393 +/- 75%, respectively. The maximal glycogenolytic rate increased significantly more in the cortisol group than in the saline group, accounting for the difference in glucose production. These results suggest that, even during chronic hypercortisolemia, acute insulin deficiency has more pronounced effects on glycogenolysis than gluconeogenesis.
本研究旨在进一步探究急性选择性胰岛素缺乏对清醒过夜禁食犬慢性生理性高皮质醇血症期间糖原分解和糖异生的影响。在80分钟的示踪剂和染料平衡期以及40分钟的基础期后，在180分钟的实验期内通过外周输注生长抑素（0.8微克·千克⁻¹·分钟⁻¹）并经门静脉基础替代胰高血糖素（0.65纳克·千克⁻¹·分钟⁻¹）来造成选择性胰岛素缺乏。在皮质醇组（n = 5）中，在实验前5天开始持续输注氢化可的松（3.5微克·千克⁻¹·分钟⁻¹）。在生理盐水组（n = 5）中，未输注皮质醇。使用[3-³H]葡萄糖、[U-¹⁴C]丙氨酸和吲哚菁绿染料，采用示踪剂和动静脉差技术评估葡萄糖生成和糖异生。在生理盐水组选择性胰岛素缺乏期间，动脉血浆葡萄糖水平（Glc）从109±2毫克/分升升至285±19毫克/分升；葡萄糖生成从2.7±0.2毫克·千克⁻¹·分钟⁻¹增至4.5±0.3毫克·千克⁻¹·分钟⁻¹。糖异生效率以及丙氨酸向葡萄糖的转化率（Conv）分别增加了300±55%和356±67%。在皮质醇组选择性胰岛素缺乏期间，Glc从117±3毫克/分升升至373±50毫克/分升；葡萄糖生成从3.3±0.5毫克·千克⁻¹·分钟⁻¹增至6.9±0.7毫克·千克⁻¹·分钟⁻¹。糖异生效率和Conv分别增加了268±41%和393±75%。皮质醇组的最大糖原分解速率显著高于生理盐水组，这解释了葡萄糖生成的差异。这些结果表明，即使在慢性高皮质醇血症期间，急性胰岛素缺乏对糖原分解的影响比对糖异生的影响更为显著。
