Sealy Center on Aging, University of Texas Medical Branch, Galveston, Texas, USA.
Diabetes. 2010 Nov;59(11):2764-71. doi: 10.2337/db10-0415. Epub 2010 Aug 19.
Skeletal muscle protein metabolism is resistant to the anabolic action of insulin in healthy, nondiabetic older adults. This defect is associated with impaired insulin-induced vasodilation and mTORC1 signaling. We hypothesized that, in older subjects, pharmacological restoration of insulin-induced capillary recruitment would improve the response of muscle protein synthesis and anabolism to insulin.
Twelve healthy, nondiabetic older subjects (71 ± 2 years) were randomized to two groups. Subjects were studied at baseline and during local infusion in one leg of insulin alone (Control) or insulin plus sodium nitroprusside (SNP) at variable rate to double leg blood flow. We measured leg blood flow by dye dilution; muscle microvascular perfusion with contrast enhanced ultrasound; Akt/mTORC1 signaling by Western blotting; and muscle protein synthesis, amino acid, and glucose kinetics using stable isotope methodologies.
There were no baseline differences between groups. Blood flow, muscle perfusion, phenylalanine delivery to the leg, and intracellular availability of phenylalanine increased significantly (P < 0.05) in SNP only. Akt phosphorylation increased in both groups but increased more in SNP (P < 0.05). Muscle protein synthesis and net balance (nmol · min(-1) · 100 ml · leg(-1)) increased significantly (P < 0.05) in SNP (synthesis, 43 ± 6 to 129 ± 25; net balance, -16 ± 3 to 26 ± 12) but not in Control (synthesis, 41 ± 10 to 53 ± 8; net balance, -17 ± 3 to -2 ± 3).
Pharmacological enhancement of muscle perfusion and amino acid availability during hyperinsulinemia improves the muscle protein anabolic effect of insulin in older adults.
在健康的非糖尿病老年人群中，骨骼肌蛋白代谢对胰岛素的合成代谢作用具有抗性。这种缺陷与胰岛素诱导的血管舒张和 mTORC1 信号受损有关。我们假设，在老年受试者中，药理学恢复胰岛素诱导的毛细血管募集将改善肌肉蛋白合成和合成代谢对胰岛素的反应。
12 名健康的非糖尿病老年受试者（71 ± 2 岁）被随机分为两组。在基础状态和一条腿单独输注胰岛素（对照）或胰岛素加硝普钠（SNP）以改变速率使双下肢血流加倍的情况下，对受试者进行了研究。我们通过染料稀释测量腿部血流；通过对比增强超声测量肌肉微血管灌注；通过 Western 印迹测量 Akt/mTORC1 信号；并使用稳定同位素方法测量肌肉蛋白合成、氨基酸和葡萄糖动力学。
两组之间在基线时没有差异。SNP 组的血流量、肌肉灌注、苯丙氨酸向腿部的输送以及细胞内苯丙氨酸的可用性均显著增加（P < 0.05）。Akt 磷酸化在两组中均增加，但 SNP 组增加更多（P < 0.05）。SNP 组的肌肉蛋白合成和净平衡（nmol·min-1·100ml-1·腿-1）显著增加（P < 0.05）（合成，43 ± 6 至 129 ± 25；净平衡，-16 ± 3 至 26 ± 12），但对照组无显著增加（合成，41 ± 10 至 53 ± 8；净平衡，-17 ± 3 至-2 ± 3）。
在高胰岛素血症期间，增强肌肉灌注和氨基酸可用性的药理学方法可改善胰岛素对老年人群的肌肉蛋白合成代谢作用。
