Jacob R, Barrett E, Plewe G, Fagin K D, Sherwin R S
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
J Clin Invest. 1989 May;83(5):1717-23. doi: 10.1172/JCI114072.
To elucidate the acute metabolic actions of insulin-like growth factor I (IGF-I), we administered a primed (250 micrograms/kg), continuous (5 micrograms/kg.min) infusion of human recombinant (Thr 59) IGF-I or saline to awake, chronically catheterized 24-h fasted rats for 90 min. IGF-I was also infused while maintaining euglycemia (glucose clamp technique) and its effects were compared to those of insulin. IGF-I infusion caused a twofold rise in IGF-I levels and a 75-85% decrease in plasma insulin. When IGF-I alone was given, plasma glucose fell by 30-40 mg/dl (P less than 0.005) due to a transient twofold increase (P less than 0.05) in glucose uptake; hepatic glucose production and plasma FFA levels remained unchanged. IGF-I infusion with maintenance of euglycemia produced a sustained rise in glucose uptake and a marked stimulation of [3-3H]glucose incorporation into tissue glycogen, but still failed to suppress glucose production and FFA levels. IGF-I also produced a generalized 30-40% reduction in plasma amino acids, regardless of whether or not hypoglycemia was prevented. This was associated with a decrease in leucine flux and a decline in the incorporation of [1-14C]leucine into muscle and liver protein (P less than 0.05). When insulin was infused in a dosage that mimicked the rise in glucose uptake seen with IGF-I, nearly identical changes in amino acid metabolism occurred. However, insulin suppressed glucose production by 65% and FFA levels by 40% (P less than 0.001). Furthermore, insulin was less effective than IGF-I in promoting glycogen synthesis. We conclude that (a) IGF-I produces hypoglycemia by selectively enhancing glucose uptake; (b) IGF-I is relatively ineffective in suppressing hepatic glucose production or FFA levels; and (c) IGF-I, like insulin, lowers circulating amino acids by reducing protein breakdown rather than by stimulating protein synthesis. Thus, IGF-I's metabolic actions in fasted rats are readily distinguished from insulin.
为阐明胰岛素样生长因子I（IGF-I）的急性代谢作用，我们对清醒、长期插管且禁食24小时的大鼠持续输注人重组（苏氨酸59）IGF-I或生理盐水90分钟，其中初始剂量为250微克/千克，持续剂量为5微克/千克·分钟。在维持血糖正常（葡萄糖钳夹技术）的同时也输注IGF-I，并将其作用与胰岛素的作用进行比较。输注IGF-I导致IGF-I水平升高两倍，血浆胰岛素水平降低75 - 85%。单独给予IGF-I时，由于葡萄糖摄取瞬间增加两倍（P < 0.05），血浆葡萄糖下降30 - 40毫克/分升（P < 0.005）；肝葡萄糖生成和血浆游离脂肪酸水平保持不变。在维持血糖正常的情况下输注IGF-I会使葡萄糖摄取持续增加，并显著刺激[3-3H]葡萄糖掺入组织糖原，但仍无法抑制葡萄糖生成和游离脂肪酸水平。无论是否预防低血糖，IGF-I还会使血浆氨基酸普遍降低30 - 40%。这与亮氨酸通量减少以及[1-14C]亮氨酸掺入肌肉和肝脏蛋白质减少有关（P < 0.05）。当以模拟IGF-I引起的葡萄糖摄取增加的剂量输注胰岛素时，氨基酸代谢发生几乎相同的变化。然而，胰岛素使葡萄糖生成抑制65%，游离脂肪酸水平抑制40%（P < 0.001）。此外，胰岛素在促进糖原合成方面不如IGF-I有效。我们得出结论：（a）IGF-I通过选择性增强葡萄糖摄取导致低血糖；（b）IGF-I在抑制肝葡萄糖生成或游离脂肪酸水平方面相对无效；（c）IGF-I与胰岛素一样，通过减少蛋白质分解而非刺激蛋白质合成来降低循环氨基酸水平。因此，禁食大鼠中IGF-I的代谢作用与胰岛素明显不同。
