University of Nottingham, School of Graduate Entry Medicine and Health, Derby, United Kingdom.
Am J Clin Nutr. 2009 Nov;90(5):1343-50. doi: 10.3945/ajcn.2009.27543. Epub 2009 Sep 9.
Reduced postprandial muscle proteolysis is mainly due to increased insulin availability. Whether rates of proteolysis in response to low physiologic doses of insulin are affected by aging is unknown.
We tested the hypothesis that suppression of leg protein breakdown (LPB) by insulin is blunted in older subjects, together with blunted activation of Akt-protein kinase B (PKB).
Groups of 8 young [mean (+/-SD) age: 24.5 +/- 1.8 y] and older (65.0 +/- 1.3 y) participants were studied during euglycemic (5 mmol/L), isoaminoacidemic (blood leucine approximately 120 micromol/L) clamp procedures at plasma insulin concentrations of approximately 5 and approximately 15 microIU/mL for 1.5 h. Leg amino acid balance, whole-leg protein turnover (as dilution of amino acid tracers), and muscle protein synthesis were measured with D(5)-phenylalanine and [1,2-(13)C(2)]leucine. The kinase activity of muscle Akt-PKB and the extent of phosphorylation of signaling proteins associated with the mTOR (mammalian target of rapamycin) pathway were measured before and after the clamp procedures.
Basal LPB rates were not different between groups (66 +/- 11 compared with 51 +/- 10 nmol leucine x 100 mL leg(-1) x min(-1) and 30 +/- 5 compared with 24 +/- 4 nmol phenylalanine x 100 mL leg(-1) x min(-1) in young and older groups, respectively). However, although insulin at approximately 15 microIU/mL lowered LPB by 47% in the young subjects (P < 0.05) and abolished the negative leg amino acid balance, this caused only a 12% fall (P > 0.05) in the older group. Akt-PKB activity mirrored decreases in LPB. No differences were seen in muscle protein synthesis or associated anabolic signaling phosphoproteins.
At moderate availability, the effect of insulin on LPB is diminished in older human beings, and this effect may be mediated through blunted Akt-PKB activation.
餐后肌肉蛋白分解减少主要是由于胰岛素的可用性增加。目前尚不清楚对低生理剂量胰岛素的反应中蛋白分解率是否会因衰老而受到影响。
我们检验了这样一个假设，即在老年人中，胰岛素对腿部蛋白分解（LPB）的抑制作用减弱，同时 Akt-蛋白激酶 B（PKB）的激活作用减弱。
在血糖（5mmol/L）、等氨基酸血症（血液亮氨酸约 120μmol/L）的情况下，对 8 名年轻（平均[+/-SD]年龄：24.5[+/-1.8]岁）和年老（65.0[+/-1.3]岁）的参与者进行了分组研究。在大约 5 和大约 15μIU/mL 的血浆胰岛素浓度下进行 1.5 小时。通过 D（5）-苯丙氨酸和[1,2-（13）C2]亮氨酸测量腿部氨基酸平衡、整个腿部蛋白质周转率（作为氨基酸示踪剂的稀释度）和肌肉蛋白质合成。在钳夹过程前后测量肌肉 Akt-PKB 的激酶活性和与 mTOR（哺乳动物雷帕霉素靶蛋白）途径相关的信号蛋白的磷酸化程度。
两组的基础 LPB 率没有差异（年轻组为 66[+/-11]与 51[+/-10]nmol 亮氨酸 x 100 mL 腿[-1] x min[-1]，老年组为 30[+/-5]与 24[+/-4]nmol 苯丙氨酸 x 100 mL 腿[-1] x min[-1]）。然而，尽管在年轻组中，约 15μIU/mL 的胰岛素将 LPB 降低了 47%（P<0.05）并消除了负的腿部氨基酸平衡，但在老年组中仅引起 12%的下降（P>0.05）。Akt-PKB 活性反映了 LPB 的减少。肌肉蛋白质合成或相关的合成代谢信号磷酸化蛋白没有差异。
在中等可用性下，胰岛素对 LPB 的作用在老年人中减弱，这种作用可能是通过 Akt-PKB 激活减弱介导的。
