Douglas R G, Gluckman P D, Ball K, Breier B, Shaw J H
Department of Surgery, University of Auckland, New Zealand.
J Clin Invest. 1991 Aug;88(2):614-22. doi: 10.1172/JCI115346.
In vivo effects of 300-min infusions of recombinant insulinlike growth factor I (IGF-I) and IGF-II on glucose and protein metabolism have been investigated in awake, fasted lambs. Two doses of recombinant human (rh) IGF-I were infused: 6.7 nmol/kg.h, which induced hypoglycemia, and 2.0 nmol/kg.h, which did not. The effects were compared with an insulin infusion (0.17 nmol/kg.h) that had the same hypoglycemic potential as the high dose rhIGF-I infusion. rhIGF-II was infused at a rate of 6.7 nmol/kg.h. Primed constant infusions of isotopically labeled glucose, urea and leucine tracers were used to determine glucose and protein kinetics. rhIGF-I lowered blood glucose by increasing the rate of glucose clearance (P less than 0.01), in contrast to insulin, which both increased clearance and reduced glucose production. Net protein loss was reduced after infusion of low and high dose rhIGF-I and insulin by 11% (P less than 0.05), 15% (P less than 0.01), and 12% (P less than 0.05), respectively. rhIGF-II infusion did not alter the rate of net protein loss. In contrast to insulin, high dose rhIGF-I infusion increased the rate of protein synthesis in skeletal (P less than 0.05) and cardiac muscle (P less than 0.01) and in hepatic tissue (P less than 0.05). We conclude that (a) protein metabolism is more sensitive than glucose metabolism to rhIGF-I infusion, as protein loss was reduced by an rhIGF-I infusion that did not alter glucose kinetics; (b) protein synthesis is increased by rhIGF-I infusion but not by insulin infusion; and (c) rhIGF-II is a less effective anabolic agent than rhIGF-I. We speculate that the effects of rhIGF-I on protein metabolism are not mediated by insulin receptors.
在清醒、禁食的羔羊中，研究了300分钟输注重组胰岛素样生长因子I（IGF-I）和IGF-II对葡萄糖和蛋白质代谢的体内效应。输注了两种剂量的重组人（rh）IGF-I：6.7 nmol/kg·h，可诱导低血糖；2.0 nmol/kg·h，不会诱导低血糖。将这些效应与具有与高剂量rhIGF-I输注相同降血糖潜力的胰岛素输注（0.17 nmol/kg·h）进行比较。rhIGF-II以6.7 nmol/kg·h的速率输注。使用同位素标记的葡萄糖、尿素和亮氨酸示踪剂的预充式持续输注来测定葡萄糖和蛋白质动力学。与胰岛素不同，rhIGF-I通过增加葡萄糖清除率降低血糖（P<0.01），胰岛素既增加清除率又减少葡萄糖生成。输注低剂量和高剂量rhIGF-I以及胰岛素后，净蛋白质损失分别减少了11%（P<0.05）、15%（P<0.01）和12%（P<0.05）。rhIGF-II输注未改变净蛋白质损失速率。与胰岛素不同，高剂量rhIGF-I输注增加了骨骼肌（P<0.05）、心肌（P<0.01）和肝组织（P<0.05）中的蛋白质合成速率。我们得出结论：（a）蛋白质代谢比葡萄糖代谢对rhIGF-I输注更敏感，因为未改变葡萄糖动力学的rhIGF-I输注减少了蛋白质损失；（b）rhIGF-I输注增加蛋白质合成，但胰岛素输注不增加；（c）rhIGF-II作为合成代谢剂的效果不如rhIGF-I。我们推测rhIGF-I对蛋白质代谢的作用不是由胰岛素受体介导的。
