Effect of insulin on human skeletal muscle protein synthesis is modulated by insulin-induced changes in muscle blood flow and amino acid availability
Effect of insulin on human skeletal muscle protein synthesis is modulated by insulin-induced changes in muscle blood flow and amino acid availability
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DOI：
10.1152/ajpendo.00271.2005
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发表时间：
2006-10-01
影响因子：
5.1
通讯作者：
Volpi, Elena
中科院分区：
文献类型：
--
作者：
Fujita, Satoshi;Rasmussen, Blake B.;Volpi, Elena
胰岛素促进肌肉生长，但目前尚不清楚它是否刺激人体肌肉蛋白质合成。我们假设胰岛素只有在增加肌肉氨基酸可用性的情况下才能增加肌肉蛋白质合成。我们使用稳定同位素方法测量了19名年轻健康受试者在基线和在低（LD，0.05），中（ID，0.15）或高（HD，0.30 mU（.））胰岛素输注期间的肌肉蛋白质和氨基酸代谢。min（-1）（.）100 ml（-1））剂量。局部输注胰岛素以在生理范围内诱导肌肉高胰岛素血症，同时最大限度地减少全身效应。使用稳定同位素和肌肉活检评估了整个腿部的蛋白质和氨基酸动力学。LD不影响苯丙氨酸向肌肉的输送（与基线相比变化-9 +/-18%）、肌肉蛋白质合成（16 +/-26%）、分解或净平衡。ID增加（P < 0.05）苯丙氨酸递送（+63 +/-38%）、肌肉蛋白质合成（+157 +/-54%）和净蛋白质平衡，而分解没有变化。HD没有改变苯丙氨酸递送（+12 +/- 11%）或肌肉蛋白质合成（+9 +/- 19%），并减少肌肉蛋白质分解（-17 +/- 15%），从而改善肌肉蛋白质净平衡，但程度低于ID。肌肉蛋白质合成的变化与肌肉血流量和苯丙氨酸递送和可用性的变化密切相关。总之，生理性高胰岛素血症促进肌肉蛋白质合成，只要它伴随着增加肌肉血流量，氨基酸输送和可用性。
Insulin promotes muscle anabolism, but it is still unclear whether it stimulates muscle protein synthesis in humans. We hypothesized that insulin can increase muscle protein synthesis only if it increases muscle amino acid availability. We measured muscle protein and amino acid metabolism using stable-isotope methodologies in 19 young healthy subjects at baseline and during insulin infusion in one leg at low (LD, 0.05), intermediate (ID, 0.15), or high (HD, 0.30 mU (.) min(-1) (.) 100 ml(-1)) doses. Insulin was infused locally to induce muscle hyperinsulinemia within the physiological range while minimizing the systemic effects. Protein and amino acid kinetics across the leg were assessed using stable isotopes and muscle biopsies. The LD did not affect phenylalanine delivery to the muscle (-9 +/- 18% change over baseline), muscle protein synthesis (16 +/- 26%), breakdown, or net balance. The ID increased (P < 0.05) phenylalanine delivery (+63 +/- 38%), muscle protein synthesis (+157 +/- 54%), and net protein balance, with no change in breakdown. The HD did not change phenylalanine delivery (+12 +/- 11%) or muscle protein synthesis (+9 +/- 19%), and reduced muscle protein breakdown (-17 +/- 15%), thus improving net muscle protein balance but to a lesser degree than the ID. Changes in muscle protein synthesis were strongly associated with changes in muscle blood flow and phenylalanine delivery and availability. In conclusion, physiological hyperinsulinemia promotes muscle protein synthesis as long as it concomitantly increases muscle blood flow, amino acid delivery and availability.