Zinker B A, Wilson R, Wasserman D H
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0615, USA.
Am J Physiol. 1995 Jun;268(6 Pt 1):E1174-83. doi: 10.1152/ajpendo.1995.268.6.E1174.
Reduced O2 availability, as might occur under some physiological and pathological conditions, stimulates insulin and glucagon release and increases glucose fluxes and muscle carbohydrate metabolism. The aim of this study was to determine the role of reduced PO2, independent of changes in glucagon and insulin. In six dogs, in paired studies separated by 2 wk, glucagon and insulin levels were fixed throughout by infusion of somatostatin with basal intraportal glucagon and insulin replacement. A control period was followed by 90 min of breathing 21% (NO) or 8% (LO) O2. Isotopic and arteriovenous methods were used to assess carbohydrate metabolism. Measured variables were constant over time in NO. Arterial PO2 (Pao2) was approximately 100 mmHg in NO and approximately 30 mmHg in LO, resulting in a 50% fall in O2 content. Insulin, glucagon, and catecholamine levels were similar in NO and LO. Cortisol was significantly increased in LO. Arterial glucose was unchanged in both groups. In the last 45 min of the experimental period in LO, 1) glucose production (14 +/- 1 to 18 +/- 1 mumol.kg-1.min-1), glucose disappearance (15 +/- 1 to 17 +/- 1 mumol.kg-1.min-1), and net hepatic glucose output (11 +/- 1 to 15 +/- 1 mumol.kg-1.min-1) rose, 2) limb pyruvate oxidation (11 +/- 2 to 24 +/- 5 mumol/min) and estimated glycogenolysis (9 +/- 3 to 42 +/- 9 mumol/min) increased, 3) percentages of CO2 from limb pyruvate and glucose increased, and percentage of lactate from blood glucose decreased, and 4) arterial blood lactate was approximately 100% more, although net limb and hepatic lactate balances were unaltered, which suggests that neither liver nor muscle is the source of increased blood lactate. Comparison of these results with our previous study [Zinker et al. Am. J. Physiol. 266 (Endocrinol. Metab. 29): E921-E929, 1994] shows that the response to reduced PaO2, although present, is reduced when glucagon and insulin levels are fixed at basal. The majority of stimulation of glucose production by decreased PaO2 is still present when pancreatic hormones are clamped at basal, while the response by the hindlimb tissues is greatly reduced.
在某些生理和病理条件下可能出现的氧供应减少，会刺激胰岛素和胰高血糖素的释放，并增加葡萄糖通量和肌肉碳水化合物代谢。本研究的目的是确定降低的氧分压的作用，而不考虑胰高血糖素和胰岛素的变化。在6只狗身上，在间隔2周的配对研究中，通过输注生长抑素并补充基础门静脉内的胰高血糖素和胰岛素，使胰高血糖素和胰岛素水平在整个过程中保持固定。在一个对照期之后，进行90分钟的吸入21%（正常氧浓度，NO）或8%（低氧浓度，LO）氧气的实验。采用同位素法和动静脉法评估碳水化合物代谢。在正常氧浓度组中，测量变量随时间保持恒定。正常氧浓度组的动脉血氧分压（Pao2）约为100 mmHg，低氧浓度组约为30 mmHg，导致氧含量下降50%。正常氧浓度组和低氧浓度组的胰岛素、胰高血糖素和儿茶酚胺水平相似。低氧浓度组的皮质醇显著升高。两组的动脉血糖均未改变。在低氧浓度组实验期的最后45分钟内，1）葡萄糖生成（从14±1至18±1 μmol·kg⁻¹·min⁻¹）、葡萄糖消失（从15±1至17±1 μmol·kg⁻¹·min⁻¹）和肝脏净葡萄糖输出（从11±1至15±1 μmol·kg⁻¹·min⁻¹）增加，2）肢体丙酮酸氧化（从11±2至24±5 μmol/min）和估计的糖原分解（从9±3至42±9 μmol/min）增加，3）来自肢体丙酮酸和葡萄糖的二氧化碳百分比增加，来自血糖的乳酸百分比降低，4）动脉血乳酸增加约100%，尽管肢体和肝脏的乳酸净平衡未改变，这表明肝脏和肌肉都不是血乳酸增加的来源。将这些结果与我们之前的研究[津克等人。《美国生理学杂志》266（内分泌与代谢29）：E921 - E929，1994]进行比较表明，当胰高血糖素和胰岛素水平固定在基础水平时，尽管对降低的氧分压仍有反应，但反应减弱。当胰腺激素钳制在基础水平时，氧分压降低对葡萄糖生成的大部分刺激仍然存在，而后肢组织的反应则大大减弱。
