Nygren J, Thorell A, Brismar K, Karpe F, Ljungqvist O
Department of Surgery, Gustaf V Research Institute, Karolinska Hospital, Stockholm, Sweden.
Nutrition. 1997 Nov-Dec;13(11-12):945-51. doi: 10.1016/s0899-9007(97)00335-3.
Hyperinsulinemic, normoglycemic clamps were performed before and after 24 h of either hypocaloric nutrition or bed rest in healthy subjects. Decreased insulin sensitivity and insulin-like growth factor-I (IGF-I) bioavalibility, as measured by the serum IGF-I/insulin-like growth factor binding protein-1 (IGFBP-1) ratio, was found after fasting, whereas no metabolic changes were found after bed rest. Glucagon seems to be a key regulator of IGFBP-1 after brief hypocaloric nutrition. Hypocaloric nutrition and immobilization may add to the catabolic response to surgery and other trauma. Presently, six healthy subjects were studied before and after a 24-h period of hypocaloric nutrition (200 kcal/24 h, fast) or immobilization (bed rest) using the hyperinsulinemic (0.8 mU.kg-1.min-1), normoglycemic (4.5 mmol/L) clamp, indirect calorimetry, and circulating levels of substrates and hormones. After fast, body weight decreased (P < 0.05), and nitrogen balance was negative (-10 +/- 1 g urea nitrogen/24 h). Basal levels of free fatty acids, glucagon, and IGFBP-1 increased (P < 0.05), whereas c-peptide levels and the IGF-I/IGFBP-1 ratio decreased (P < 0.05). However, no change was found in basal levels of IGF-1 or substrate oxidation. Furthermore, changes (%) in basal levels of glucagon after fast correlated to IGFBP-1 (r = 1.0, P < 0.05), whereas the suppressibility of IGFBP-1 by insulin was maintained at normal levels. During clamps, glucose infusion rates (GIR) decreased after fast (-43 +/- 13%, mean +/- SEM, P < 0.001). Although not significantly, clamp levels of fat oxidation tended to increase and glucose oxidation tended to decrease. Levels of IGFBP-1 during clamps were higher as compared with the control clamp (P < 0.05). No adverse metabolic changes were seen after bed rest, and no change in GIR during clamps were seen as compared with the control measurement (0 +/- 14%). After brief hypocaloric nutrition, insulin sensitivity is reduced, whereas IGF-I bioavalibility is reduced by an increase in levels of IGFBP-1. Glucagon seems to contribute to the increase in IGFBP-1 during these conditions.
在健康受试者中，分别于低热量营养或卧床休息24小时前后进行高胰岛素正常血糖钳夹试验。通过血清胰岛素样生长因子-I（IGF-I）/胰岛素样生长因子结合蛋白-1（IGFBP-1）比值测定发现，禁食后胰岛素敏感性和IGF-I生物利用度降低，而卧床休息后未发现代谢变化。在短暂低热量营养后，胰高血糖素似乎是IGFBP-1的关键调节因子。低热量营养和制动可能会加重手术及其他创伤后的分解代谢反应。目前，对6名健康受试者在进行24小时低热量营养（200千卡/24小时，禁食）或制动（卧床休息）前后，采用高胰岛素（0.8毫单位·千克-1·分钟-1）、正常血糖（4.5毫摩尔/升）钳夹试验、间接测热法以及底物和激素的循环水平进行了研究。禁食后，体重下降（P<0.05），氮平衡为负（-10±1克尿素氮/24小时）。游离脂肪酸、胰高血糖素和IGFBP-1的基础水平升高（P<0.05），而C肽水平和IGF-I/IGFBP-1比值降低（P<0.05）。然而，IGF-1基础水平或底物氧化未发现变化。此外，禁食后胰高血糖素基础水平的变化（%）与IGFBP-1相关（r = 1.0，P<0.05），而胰岛素对IGFBP-1的抑制作用维持在正常水平。在钳夹试验期间，禁食后葡萄糖输注率（GIR）降低（-43±13%，平均值±标准误，P<0.001）。虽然无显著差异，但钳夹试验期间脂肪氧化水平有升高趋势，葡萄糖氧化水平有降低趋势。与对照钳夹试验相比，钳夹试验期间IGFBP-1水平更高（P<0.05）。卧床休息后未观察到不良代谢变化，与对照测量相比（0±14%），钳夹试验期间GIR无变化。在短暂低热量营养后，胰岛素敏感性降低，而IGF-I生物利用度因IGFBP-1水平升高而降低。在这些情况下，胰高血糖素似乎促成了IGFBP-1的升高。
