Glucagon-like peptide 1 infusions overcome anabolic resistance to feeding in older human muscle.
Glucagon-like peptide 1 infusions overcome anabolic resistance to feeding in older human muscle.
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DOI：
10.1111/acel.13202
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发表时间：
2020-09
期刊：
影响因子：
7.8
通讯作者：
Atherton PJ
中科院分区：
文献类型：
--
作者：
Abdulla H;Phillips BE;Wilkinson DJ;Limb M;Jandova T;Bass JJ;Rankin D;Cegielski J;Sayda M;Crossland H;Williams JP;Smith K;Idris I;Atherton PJ
尽管胰高血糖素样肽-1（GLP-1）具有已知的胰岛素非依赖性作用，但尚未在进食状态下或在老年背景下探索其在肌肉蛋白质周转中的作用，此时胰岛素敏感性和蛋白质代谢下降，以及肌肉质量和功能丧失。在一项交叉试验中研究了8名老年男性（71 ± 1岁，平均值± SEM）。在餐后3小时胰岛素（~30 mIU ml-1）和葡萄糖（7-7.5 mM）钳夹前，在3小时内进行基线测量，同时静脉输注奥曲肽和Vamin 14（± GLP-1输注）。四个肌肉活检，并通过掺入13 C6苯丙氨酸和动静脉平衡动力学，使用质谱定量肌肉蛋白质周转。通过超声和免疫印迹法合成代谢信号评估腿部大血管和微血管流量。通过ELISA测量GLP-1和胰岛素。与非GLP-1试验相比，GLP-1增加了肌肉蛋白质合成（MPS;空腹：0.058 ± 0.004% hr−1 vs.餐后：0.102 ± 0.005% hr−1，p < 0.01）。肌肉蛋白质分解（MPB）减少整个钳夹期间，而整个腿的净蛋白质平衡成为积极的两组。钳夹未改变总股腿血流量;然而，两组的肌肉微血管血流量（MBF）均显著升高，GLP-1组的程度显著更高（MBF：5 ± 2倍变化vs. 1.9 ± 1倍变化+GLP-1和−GLP-1，p < 0.01）。两项试验中Akt‐mTOR信号传导的激活相似。在餐后胰岛素高氨基酸钳夹期间，GLP-1输注显著增强餐后微血管灌注，并进一步刺激肌肉蛋白质代谢，主要是通过增加MPS。餐后钳夹期间GLP-1输注后肌肉肌原纤维蛋白合成增加
Despite its known insulin‐independent effects, glucagon‐like peptide‐1 (GLP‐1) role in muscle protein turnover has not been explored under fed‐state conditions or in the context of older age, when declines in insulin sensitivity and protein anabolism, as well as losses of muscle mass and function, occur. Eight older‐aged men (71 ± 1 year, mean ± SEM) were studied in a crossover trial. Baseline measures were taken over 3 hr, prior to a 3 hr postprandial insulin (~30 mIU ml−1) and glucose (7–7.5 mM) clamp, alongside I.V. infusions of octreotide and Vamin 14 (±infusions of GLP‐1). Four muscle biopsies were taken, and muscle protein turnover was quantified via incorporation of 13C6 phenylalanine and arteriovenous balance kinetics, using mass spectrometry. Leg macro‐ and microvascular flow was assessed via ultrasound and anabolic signalling by immunoblotting. GLP‐1 and insulin were measured by ELISA. GLP‐1 augmented muscle protein synthesis (MPS; fasted: 0.058 ± 0.004% hr−1 vs. postprandial: 0.102 ± 0.005% hr−1, p < 0.01), in comparison with non‐GLP‐1 trials. Muscle protein breakdown (MPB) was reduced throughout clamp period, while net protein balance across the leg became positive in both groups. Total femoral leg blood flow was unchanged by the clamp; however, muscle microvascular blood flow (MBF) was significantly elevated in both groups, and to a significantly greater extent in the GLP‐1 group (MBF: 5 ± 2 vs. 1.9 ± 1 fold change +GLP‐1 and −GLP‐1, respectively, p < 0.01). Activation of the Akt‐mTOR signalling was similar across both trials. GLP‐1 infusion markedly enhanced postprandial microvascular perfusion and further stimulated muscle protein metabolism, primarily through increased MPS, during a postprandial insulin hyperaminoacidaemic clamp. Muscle myofibrillar protein synthesis rises following GLP‐1 infusion during postprandial clamp
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氨基酸和胰岛素对人类肌肉中信号传导，泛素连接酶和蛋白质更新的作用之间的分离。
DOI：
10.1152/ajpendo.90411.2008
发表时间：
2008-09
期刊：
American journal of physiology. Endocrinology and metabolism
影响因子：
--
作者：
Greenhaff PL;Karagounis LG;Peirce N;Simpson EJ;Hazell M;Layfield R;Wackerhage H;Smith K;Atherton P;Selby A;Rennie MJ
通讯作者：
Rennie MJ
影响因子：
7.1
作者：
Atherton, Philip J.;Etheridge, Timothy;Rennie, Michael J.
通讯作者：
Rennie, Michael J.
影响因子：
5.5
作者：
Churchward-Venne, Tyler A.;Burd, Nicholas A.;Phillips, Stuart M.
通讯作者：
Phillips, Stuart M.
DOI：
10.1093/gerona/glu103
发表时间：
2015-01-01
影响因子：
5.1
作者：
Moore, Daniel R.;Churchward-Venne, Tyler A.;Phillips, Stuart M.
通讯作者：
Phillips, Stuart M.
影响因子：
4
作者：
ELLIOTT, RM;MORGAN, LM;MARKS, V
通讯作者：
MARKS, V