Walton P E, Dunshea F R, Ballard F J
Cooperative Research Centre for Tissue Growth and Repair, Adelaide, Australia.
Prog Growth Factor Res. 1995;6(2-4):385-95. doi: 10.1016/0955-2235(95)00007-0.
IGF-I analogues that bind poorly to IGFBPs are substantially more potent than IGF-I at stimulating growth in rats. However, rodents differ from other mammals because they contain only minimal circulating levels of IGF-II and they are poorly responsive to GH. In this report we review a series of experiments carried out in pigs, a species that is both GH responsive and has high blood concentrations of IGF-II. Intravenous bolus administration of IGFs to 55 kg pigs depressed blood glucose with the potency greatest for analogues such as des (1-3) IGF-I, R3IGF-I and Long R3IGF-I that showed the weakest binding to pig IGFBP-3, a similar efficacy pattern to that reported in the rat. Chronic subcutaneous administration of Long R3IGF-I, however, reduced growth rates, led to a depression in food intake and lowered concentrations of IGF-I, IGF-II and IGFBP-3. IGF-I itself depressed IGF-II concentrations and did not stimulate growth. Subcutaneous infusion of IGFs over a 3-day period, also in 55 kg pigs, demonstrated that analogues that bound least well to IGFBP-3 were the most effective at reducing the concentration of this binding protein, suggesting that the inhibition of growth was related to the depression of IGFBP-3. On the other hand, IGF-I and Long R3IGF-I increased growth rats in neonatal pigs, especially under conditions of reduced food intake. As these anabolic effects occur at a developmental stage where the animals are insensitive to GH in a manner analogous to the situation in rats, it is plausible that the feed-back inhibition of GH secretion explains the catabolic response to IGFs in older pigs.
与胰岛素样生长因子结合蛋白（IGFBP）结合能力差的IGF-I类似物在刺激大鼠生长方面比IGF-I的效力要高得多。然而，啮齿动物与其他哺乳动物不同，因为它们循环中的IGF-II水平极低，并且对生长激素（GH）反应不佳。在本报告中，我们回顾了一系列在猪身上进行的实验，猪是一种对GH有反应且血液中IGF-II浓度很高的物种。对55公斤重的猪静脉推注IGF会降低血糖，对于与猪IGFBP-3结合最弱的类似物，如des(1-3)IGF-I、R3IGF-I和Long R3IGF-I，其效力最大，这与在大鼠中报道的效力模式相似。然而，长期皮下注射Long R3IGF-I会降低生长速度，导致采食量下降，并降低IGF-I、IGF-II和IGFBP-3的浓度。IGF-I本身会降低IGF-II的浓度，且不刺激生长。同样在55公斤重的猪身上，连续3天皮下输注IGF表明，与IGFBP-3结合最差的类似物在降低这种结合蛋白浓度方面最有效，这表明生长抑制与IGFBP-3的降低有关。另一方面，IGF-I和Long R3IGF-I增加了新生仔猪的生长，尤其是在采食量减少的情况下。由于这些合成代谢作用发生在动物对GH不敏感的发育阶段，类似于大鼠的情况，因此生长激素分泌的反馈抑制可能解释了大龄猪对IGF产生分解代谢反应的原因。
