Division of Medical Science and Graduate Entry Medicine, University of Nottingham, Royal Derby Hospital, Derby, United Kingdom; and.
Am J Physiol Endocrinol Metab. 2014 Jan 15;306(2):E168-76. doi: 10.1152/ajpendo.00440.2013. Epub 2013 Nov 26.
Skeletal muscle anabolism associated with postprandial plasma aminoacidemia and insulinemia is contingent upon amino acids (AA) and insulin crossing the microcirculation-myocyte interface. In this study, we hypothesized that increasing muscle microvascular blood volume (flow) would enhance fed-state anabolic responses in muscle protein turnover. We studied 10 young men (23.2 ± 2.1 yr) under postabsorptive and fed [iv Glamin (∼10 g AA), glucose ∼7.5 mmol/l] conditions. Methacholine was infused into the femoral artery of one leg to determine, via bilateral comparison, the effects of feeding alone vs. feeding plus pharmacological vasodilation. We measured leg blood flow (LBF; femoral artery) by Doppler ultrasound, muscle microvascular blood volume (MBV) by contrast-enhanced ultrasound (CEUS), muscle protein synthesis (MPS) and breakdown (MPB; a-v balance modeling), and net protein balance (NPB) using [1,2-(13)C2]leucine and [(2)H5]phenylalanine tracers via gas chromatography-mass spectrometry (GC-MS). Indexes of anabolic signaling/endothelial activation (e.g., Akt/mTORC1/NOS) were assessed using immunoblotting techniques. Under fed conditions, LBF (+12 ± 5%, P < 0.05), MBV (+25 ± 10%, P < 0.05), and MPS (+129 ± 33%, P < 0.05) increased. Infusion of methacholine further enhanced LBF (+126 ± 12%, P < 0.05) and MBV (+79 ± 30%, P < 0.05). Despite these radically different blood flow conditions, neither increases in MPS in response to feeding (0.04 ± 0.004 vs. 0.08 ± 0.01%/h, P < 0.05) nor improvements in NPB (-4.4 ± 2.4 vs. 16.4 ± 5.7 nmol Phe·100 ml leg(-1)·min(-1), P < 0.05) were affected by methacholine infusion (MPS 0.07 ± 0.01%/h; NPB 24.0 ± 7.7 nmol Phe·100 ml leg(-1)·min(-1)), whereas MPB was unaltered by either feeding or infusion of methacholine. Thus, enhancing LBF/MBV above that occurring naturally with feeding alone does not improve muscle anabolism.
骨骼肌的合成代谢与餐后血浆氨基酸血症和胰岛素血症有关，这取决于氨基酸（AA）和胰岛素穿过微循环-肌细胞界面。在这项研究中，我们假设增加肌肉微血管血液量（流量）会增强肌肉蛋白周转的喂养状态下的合成代谢反应。我们研究了 10 名年轻男性（23.2 ± 2.1 岁）在吸收后和喂养（静脉内 Glamin（约 10 g AA），葡萄糖约 7.5 mmol/l）状态下的情况。通过双侧比较，向一条腿的股动脉中注入甲胆碱，以确定单独喂养与喂养加药理学血管扩张的影响。我们通过多普勒超声测量腿部血流量（股动脉），通过对比增强超声（CEUS）测量肌肉微血管血液量（MBV），通过 [1,2-（13）C2]亮氨酸和 [（2）H5]苯丙氨酸示踪剂通过气相色谱-质谱法（GC-MS）测量肌肉蛋白质合成（MPS）和分解（MPB；a-v 平衡建模），并使用[1,2-（13）C2]亮氨酸和[（2）H5]苯丙氨酸示踪剂通过气相色谱-质谱法（GC-MS）测量净蛋白平衡（NPB）。使用免疫印迹技术评估合成代谢信号/内皮激活的指标（例如 Akt/mTORC1/NOS）。在喂养状态下，腿部血流量增加（+12 ± 5%，P < 0.05），MBV 增加（+25 ± 10%，P < 0.05），MPS 增加（+129 ± 33%，P < 0.05）。甲胆碱的输注进一步增加了腿部血流量（+126 ± 12%，P < 0.05）和 MBV（+79 ± 30%，P < 0.05）。尽管血液流量条件有很大差异，但喂养引起的 MPS 增加（0.04 ± 0.004 与 0.08 ± 0.01%/h，P < 0.05）或 NPB 改善（-4.4 ± 2.4 与 16.4 ± 5.7 nmol Phe·100 ml 腿-1·min-1，P < 0.05）均不受甲胆碱输注的影响（MPS 0.07 ± 0.01%/h；NPB 24.0 ± 7.7 nmol Phe·100 ml 腿-1·min-1）），而 MPB 不受喂养或甲胆碱输注的影响。因此，增加腿部血流量/MBV 超过单独喂养时自然发生的水平并不能改善肌肉合成代谢。
