Effects of GLP-1 Infusion Upon Whole-body Glucose Uptake and Skeletal Muscle Perfusion During Fed-state in Older Men.

Effects of GLP-1 Infusion Upon Whole-body Glucose Uptake and Skeletal Muscle Perfusion During Fed-state in Older Men.
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GLP-1输注对老年男性进食状态下全身葡萄糖摄取和骨骼肌灌注的影响。

DOI:
10.1210/clinem/dgac613
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发表时间:
2023-03-10
期刊:
The Journal of clinical endocrinology and metabolism
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老化的骨骼肌变得胰岛素抵抗和萎缩。激素胰高血糖素样肽1 (GLP-1)促进餐后葡萄糖摄取并增加肌肉灌注,独立于胰岛素的作用。因此,我们假设外源性GLP-1输注可以增强肌肉灌注,并对老年人进食状态钳夹期间的葡萄糖代谢产生积极影响。在一项随机交叉试验中研究了8名男性(71±1岁)。在餐后(进食状态)胰岛素和葡萄糖钳夹前采集基础血液样本,并辅以氨基酸输注,持续3小时。有鉴于此,在外周和股血管插管和基线测量后,外周静脉输注奥曲肽、胰岛素(Actrapid)、20%葡萄糖和混合氨基酸;开始或不进行股动脉GLP-1输注的Vamin 14-EF。ELISA法检测GLP-1、胰岛素、c肽水平。通过超声造影评估肌肉微血管血流。通过葡萄糖输注速率参数测定全身葡萄糖处理。与单独喂养相比,GLP-1显著增加了骨骼肌微血管血流量(分别是基础的5.0±2.1和1.9±0.7倍,P = 0.008),同时也增加了全身葡萄糖摄取(曲线下面积16.9±1.7 vs 11.4±1.8 mg/kg -1 /180分钟-1,P = 0.02±GLP)。GLP-1对全身血糖控制的有益作用是明显的,胰岛素被固定在喂食状态的水平。GLP-1进一步增强了胰岛素对老年男性全身葡萄糖摄取的影响,强调了其作为治疗靶点的作用。GLP-1增强微血管流动的作用可能也影响其他葡萄糖调节器官,反映在更大的全身葡萄糖摄取上。
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.
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