Nørrelund H, Nair K S, Jørgensen J O, Christiansen J S, Møller N
Medical Department M, Aarhus Kommunehospital, Denmark.
Diabetes. 2001 Jan;50(1):96-104. doi: 10.2337/diabetes.50.1.96.
The metabolic response to fasting involves a series of hormonal and metabolic adaptations leading to protein conservation. An increase in the serum level of growth hormone (GH) during fasting has been well substantiated. The present study was designed to test the hypothesis that GH may be a principal mediator of protein conservation during fasting and to assess the underlying mechanisms. Eight normal subjects were examined on four occasions: 1) in the basal postabsorptive state (basal), 2) after 40 h of fasting (fast), 3) after 40 h of fasting with somatostatin suppression of GH (fast-GH), and 4) after 40 h of fasting with suppression of GH and exogenous GH replacement (fast+GH). The two somatostatin experiments were identical in terms of hormone replacement (except for GH), meaning that somatostatin, insulin, glucagon and GH were administered for 28 h; during the last 4 h, substrate metabolism was investigated. Compared with the GH administration protocol, IGF-I and free IGF-I decreased 35 and 70%, respectively, during fasting without GH. Urinary urea excretion and serum urea increased when participants fasted without GH (urea excretion: basal 392 +/- 44, fast 440 +/- 32, fast-GH 609 +/- 76, and fast+GH 408 +/- 36 mmol/24 h, P < 0.05; serum urea: basal 4.6 +/- 0.1, fast 6.2 +/- 0.1, fast-GH 7.0 +/- 0.2, and fast+GH 4.3 +/- 0.2 mmol/1, P < 0.01). There was a net release of phenylalanine across the forearm, and the negative phenylalanine balance was higher during fasting with GH suppression (balance: basal 9 +/- 3, fast 15 +/- 6, fast-GH 17 +/- 4, and fast+GH 11 +/- 5 nmol/min, P < 0.05). Muscle-protein breakdown was increased among participants who fasted without GH (phenylalanine rate of appearance: basal 17 +/- 4, fast 26 +/- 9, fast-GH 33 +/- 7, fast+GH 25 +/- 6 nmol/min, P < 0.05). Levels of free fatty acids and oxidation of lipid decreased during fasting without GH (P < 0.01). In summary, we find that suppression of GH during fasting leads to a 50% increase in urea-nitrogen excretion, together with an increased net release and appearance rate of phenylalanine across the forearm. These results demonstrate that GH-possibly by maintenance of circulating concentrations of free IGF-I--is a decisive component of protein conservation during fasting and provide evidence that the underlying mechanism involves a decrease in muscle protein breakdown.
禁食的代谢反应涉及一系列激素和代谢适应过程，以实现蛋白质的保存。禁食期间血清生长激素（GH）水平升高已得到充分证实。本研究旨在验证GH可能是禁食期间蛋白质保存的主要介质这一假设，并评估其潜在机制。对8名正常受试者进行了4次检查：1）基础吸收后状态（基础状态）；2）禁食40小时后（禁食）；3）禁食40小时并使用生长抑素抑制GH后（禁食 - GH）；4）禁食40小时并抑制GH后进行外源性GH替代（禁食 + GH）。两项生长抑素实验在激素替代方面（除GH外）相同，即生长抑素、胰岛素、胰高血糖素和GH给药28小时；在最后4小时，研究底物代谢。与GH给药方案相比，在无GH的禁食期间，IGF - I和游离IGF - I分别下降了35%和70%。在无GH禁食的参与者中，尿尿素排泄和血清尿素增加（尿素排泄：基础状态392±44，禁食440±32，禁食 - GH 609±76，禁食 + GH 408±36 mmol/24小时，P < 0.05；血清尿素：基础状态4.6±0.1，禁食6.2±0.1，禁食 - GH 7.0±0.2，禁食 + GH 4.3±0.2 mmol/1，P < 0.01）。苯丙氨酸在前臂有净释放，且在抑制GH的禁食期间苯丙氨酸负平衡更高（平衡：基础状态9±3，禁食15±6，禁食 - GH 17±4，禁食 + GH 11±5 nmol/分钟，P < 0.05）。在无GH禁食的参与者中，肌肉蛋白分解增加（苯丙氨酸出现率：基础状态17±4，禁食26±9，禁食 - GH 33±7，禁食 + GH 25±6 nmol/分钟，P < 0.05）。在无GH的禁食期间，游离脂肪酸水平和脂质氧化下降（P < 0.01）。总之，我们发现禁食期间抑制GH会导致尿素氮排泄增加50%，同时前臂苯丙氨酸的净释放和出现率增加。这些结果表明，GH（可能通过维持游离IGF - I的循环浓度）是禁食期间蛋白质保存的决定性因素，并提供证据表明其潜在机制涉及肌肉蛋白分解的减少。
