MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, Centre of Metabolism, Ageing and Physiology (COMAP), Academic Unit of Injury, Recovery and Inflammation Sciences (IRIS), School of Medicine, University of Nottingham, Royal Derby Hospital, Derby DE22 3DT, UK.
Diabetes and Endocrinology Centre, University Hospitals Birmingham NHS Foundation Trust, Heartlands Hospitals, Birmingham B9 5SS, UK.
J Clin Endocrinol Metab. 2023 Mar 10;108(4):971-978. doi: 10.1210/clinem/dgac613.
Ageing skeletal muscles become both insulin resistant and atrophic. The hormone glucagon-like peptide 1 (GLP-1) facilitates postprandial glucose uptake as well as augmenting muscle perfusion, independent of insulin action. We thus hypothesized exogenous GLP-1 infusions would enhance muscle perfusion and positively affect glucose metabolism during fed-state clamps in older people.
Eight men (71 ± 1 years) were studied in a randomized crossover trial. Basal blood samples were taken before postprandial (fed-state) insulin and glucose clamps, accompanied by amino acid infusions, for 3 hours. Reflecting this, following insertions of peripheral and femoral vessels cannulae and baseline measurements, peripheral IV infusions of octreotide, insulin (Actrapid), 20% glucose, and mixed amino acids; Vamin 14-EF with or without a femoral arterial GLP-1 infusion were started. GLP-1, insulin, and C-peptide were measured by ELISA. Muscle microvascular blood flow was assessed via contrast enhanced ultrasound. Whole-body glucose handling was assayed by assessing glucose infusion rate parameters.
Skeletal muscle microvascular blood flow significantly increased in response to GLP-1 vs feeding alone (5.0 ± 2.1 vs 1.9 ± 0.7 fold-change from basal, respectively; P = 0.008), while also increasing whole-body glucose uptake (area under the curve 16.9 ± 1.7 vs 11.4 ± 1.8 mg/kg-1/180 minutes-1, P = 0.02 ± GLP, respectively).
The beneficial effects of GLP-1 on whole-body glycemic control are evident with insulin clamped at fed-state levels. GLP-1 further enhances the effects of insulin on whole-body glucose uptake in older men, underlining its role as a therapeutic target. The effects of GLP-1 in enhancing microvascular flow likely also affects other glucose-regulatory organs, reflected by greater whole-body glucose uptake.
衰老的骨骼肌既对胰岛素产生抗性又发生萎缩。激素胰高血糖素样肽 1（GLP-1）有助于餐后葡萄糖摄取，并增强肌肉灌注，而不依赖于胰岛素作用。因此，我们假设外源性 GLP-1 输注将在老年人进食状态钳夹期间增强肌肉灌注并对葡萄糖代谢产生积极影响。
8 名男性（71 ± 1 岁）参与了一项随机交叉试验研究。在进行 3 小时的餐后（进食状态）胰岛素和葡萄糖钳夹的同时，采集基础血样，进行氨基酸输注。反映这一点，在插入外周和股血管套管和基线测量后，开始外周静脉输注奥曲肽、胰岛素（Actrapid）、20%葡萄糖和混合氨基酸；或开始给予 Vamin 14-EF 加或不加股动脉 GLP-1 输注。通过 ELISA 测量 GLP-1、胰岛素和 C 肽。通过对比增强超声评估肌肉微血管血流。通过评估葡萄糖输注率参数来测定全身葡萄糖处理能力。
与单独进食相比，GLP-1 使骨骼肌微血管血流显著增加（分别从基础水平增加 5.0 ± 2.1 倍和 1.9 ± 0.7 倍；P = 0.008），同时还增加了全身葡萄糖摄取量（曲线下面积 16.9 ± 1.7 与 11.4 ± 1.8 mg/kg-1/180 分钟-1，分别为 P = 0.02 ± GLP）。
在胰岛素钳夹于进食状态水平下，GLP-1 对全身血糖控制的有益作用是明显的。GLP-1 进一步增强了胰岛素对老年男性全身葡萄糖摄取的作用，强调了其作为治疗靶点的作用。GLP-1 增强微血管血流的作用可能还会影响其他葡萄糖调节器官，这反映在全身葡萄糖摄取量的增加上。
