Tomas F M, Knowles S E, Owens P C, Read L C, Chandler C S, Gargosky S E, Ballard F J
CSIRO Division of Human Nutrition, Adelaide, South Australia.
J Endocrinol. 1991 Jan;128(1):97-105. doi: 10.1677/joe.0.1280097.
The ability of insulin-like growth factor-I (IGF-I) to protect against losses of body protein during periods of dietary nitrogen restriction has been evaluated in young rats. Recombinant human IGF-I was administered by osmotic pumps at dose rates of 0, 1.2 or 2.9 mg/kg per day over a 7-day period beginning with the transfer of animals from an 18% to a 4% protein diet. A fourth group received the potent truncated IGF-I analogue, des(1-3)IGF-I, at a dose of 1.2 mg/kg per day over a comparable 7-day period. Plasma IGF-I levels were reduced by 60% following nitrogen restriction, a reduction that was partly prevented by IGF-I administration, especially at the higher dose, but not measurably by des(1-3)IGF-I. The major IGF-binding protein circulating in blood, IGFBP-3, demonstrated a similar pattern of change. A significant (P less than 0.05) protection of body weight was achieved in the low dose IGF-I and des(1-3)IGF-I groups, but only after differences in food intake had been eliminated by analysis of covariance. Nitrogen balances were not significantly different unless analysis of covariance was used to adjust for the nitrogen intakes, whereupon all treatment groups showed improved balance, especially the animals treated with the low IGF-I dose and des(1-3)IGF-I (both P less than 0.01). The rate of muscle protein breakdown calculated from the urinary excretion of 3-methyl-histidine was not significantly altered by the treatments, but fell progressively throughout the 7 days. The fractional rate of muscle protein synthesis measured on the final day was increased by 31,26 and 21% respectively by the low and high doses of IGF-I and by des(1-3)IGF-I. Organ weights (g/kg body weight) showed no effects of IGF-I treatment except for 16% increases in the weight of kidneys in the high dose IGF-I and the des(1-3)IGF-I groups. Carcass analyses demonstrated higher water and lower fat contents (all P less than 0.01) in the same groups. These results suggest that exogenous IGF-I and especially des(1-3)IGF-I can partly protect body protein reserves during nitrogen restriction.
在幼鼠中评估了胰岛素样生长因子-I（IGF-I）在饮食氮限制期间防止机体蛋白质损失的能力。从动物从18%蛋白质饮食转为4%蛋白质饮食开始，在7天的时间里，通过渗透泵以每天0、1.2或2.9毫克/千克的剂量率给予重组人IGF-I。第四组在类似的7天时间里以每天1.2毫克/千克的剂量接受强效截短型IGF-I类似物des(1-3)IGF-I。氮限制后血浆IGF-I水平降低了60%，这种降低在一定程度上被IGF-I给药所预防，尤其是高剂量时，但des(1-3)IGF-I没有明显作用。血液中循环的主要IGF结合蛋白IGFBP-3表现出类似的变化模式。低剂量IGF-I组和des(1-3)IGF-I组体重得到了显著（P<0.05）保护，但只有在通过协方差分析消除食物摄入量差异后才出现。除非使用协方差分析来调整氮摄入量，否则氮平衡没有显著差异，此时所有治疗组的平衡都有所改善，尤其是低剂量IGF-I和des(1-3)IGF-I治疗的动物（均P<0.01）。根据3-甲基组氨酸的尿排泄量计算的肌肉蛋白质分解率没有因治疗而显著改变，但在整个7天中逐渐下降。在最后一天测量的肌肉蛋白质合成分数率分别因低剂量和高剂量IGF-I以及des(1-3)IGF-I而增加了31%、26%和21%。器官重量（克/千克体重）除了高剂量IGF-I组和des(1-3)IGF-I组肾脏重量增加16%外，未显示出IGF-I治疗的影响。胴体分析表明，相同组中水分含量较高而脂肪含量较低（均P<0.01）。这些结果表明，外源性IGF-I尤其是des(1-3)IGF-I在氮限制期间可以部分保护机体蛋白质储备。
