Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization.
Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization.
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DOI：
10.1002/jcsm.13075
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发表时间：
2022-12
期刊：
影响因子：
--
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中科院分区：
文献类型：
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卧床休息（BR）减少了全身胰岛素刺激的葡萄糖处理（GD）并改变了肌肉燃料代谢，但对从急性到慢性BR的代谢适应及其机制知之甚少，特别是当志愿者保持能量平衡时。维持能量平衡的健康男性（n = 10, 24.0±1.3岁）接受了3天的急性BR。另一个性别和体重指数相匹配的队列（n = 20, 34.2±1.8岁）接受56天的BR（慢性BR）治疗。采用高胰岛素血症血糖钳（60 mU/m2/min）测定BR前后全身胰岛素刺激GD的比率（以瘦体重归一化）。在每个钳夹之前和稳定状态期间进行间接量热法，以计算全身燃料氧化率。采用肌肉活检检测肌糖原、代谢物和细胞内脂质（IMCL）含量以及191个mRNA靶点在BR前后的表达。采用双向重复测量方差分析来检测终点测量的差异。急性BR降低了胰岛素介导的GD（前11.5±0.7 vs后9.3±0.6 mg/kg/min, P < 0.001），慢性BR后的幅度不变（前10.2±0.4 vs后7.9±0.3 mg/kg/min, P < 0.05）。这种GD的减少与急性和慢性BR后胰岛素刺激的肌糖原储存增加35%的消除是平行的。急性BR对胰岛素刺激的碳水化合物（CHO；前3.69±0.39 vs后4.34±0.22 mg/kg/min）和脂质氧化（前1.13±0.14 vs后0.59±0.11 mg/kg/min）没有影响，但慢性BR降低CHO氧化（前3.34±0.18 vs后2.72±0.13 mg/kg/min, P < 0.05），并减弱胰岛素介导的脂质氧化抑制程度（前0.60±0.07 vs后0.85±0.06 mg/kg/min, P < 0.05）。急性和慢性BR均未增加肌肉IMCL含量。急性BR后检测到大量mRNA丰度变化，慢性BR后减弱，反映了此时燃料氧化和肌糖原储存的变化。急性BR抑制胰岛素刺激的GD和储存，但在慢性BR中这种抑制程度没有进一步增加。然而，慢性BR后胰岛素介导的脂肪氧化抑制低于急性BR，并伴有钝化的CHO氧化。这些反应的并置表明，GD和储存的调节可以与底物氧化分离。此外，慢性BR后底物氧化的变化不能用IMCL积累来解释，而是通过肌肉mRNA和丙酮酸脱氢酶激酶4蛋白丰度的变化来反映，这表明肌肉收缩本身缺乏作为肌肉适应的主要信号。
Bed rest (BR) reduces whole‐body insulin‐stimulated glucose disposal (GD) and alters muscle fuel metabolism, but little is known about metabolic adaptation from acute to chronic BR nor the mechanisms involved, particularly when volunteers are maintained in energy balance. Healthy males (n = 10, 24.0 ± 1.3 years), maintained in energy balance, underwent 3‐day BR (acute BR). A second cohort matched for sex and body mass index (n = 20, 34.2 ± 1.8 years) underwent 56‐day BR (chronic BR). A hyperinsulinaemic euglycaemic clamp (60 mU/m2/min) was performed to determine rates of whole‐body insulin‐stimulated GD before and after BR (normalized to lean body mass). Indirect calorimetry was performed before and during steady state of each clamp to calculate rates of whole‐body fuel oxidation. Muscle biopsies were taken to determine muscle glycogen, metabolite and intramyocellular lipid (IMCL) contents, and the expression of 191 mRNA targets before and after BR. Two‐way repeated measures analysis of variance was used to detect differences in endpoint measures. Acute BR reduced insulin‐mediated GD (Pre 11.5 ± 0.7 vs. Post 9.3 ± 0.6 mg/kg/min, P < 0.001), which was unchanged in magnitude following chronic BR (Pre 10.2 ± 0.4 vs. Post 7.9 ± 0.3 mg/kg/min, P < 0.05). This reduction in GD was paralleled by the elimination of the 35% increase in insulin‐stimulated muscle glycogen storage following both acute and chronic BR. Acute BR had no impact on insulin‐stimulated carbohydrate (CHO; Pre 3.69 ± 0.39 vs. Post 4.34 ± 0.22 mg/kg/min) and lipid (Pre 1.13 ± 0.14 vs. Post 0.59 ± 0.11 mg/kg/min) oxidation, but chronic BR reduced CHO oxidation (Pre 3.34 ± 0.18 vs. Post 2.72 ± 0.13 mg/kg/min, P < 0.05) and blunted the magnitude of insulin‐mediated inhibition of lipid oxidation (Pre 0.60 ± 0.07 vs. Post 0.85 ± 0.06 mg/kg/min, P < 0.05). Neither acute nor chronic BR increased muscle IMCL content. Plentiful mRNA abundance changes were detected following acute BR, which waned following chronic BR and reflected changes in fuel oxidation and muscle glycogen storage at this time point. Acute BR suppressed insulin‐stimulated GD and storage, but the extent of this suppression increased no further in chronic BR. However, insulin‐mediated inhibition of fat oxidation after chronic BR was less than acute BR and was accompanied by blunted CHO oxidation. The juxtaposition of these responses shows that the regulation of GD and storage can be dissociated from substrate oxidation. Additionally, the shift in substrate oxidation after chronic BR was not explained by IMCL accumulation but reflected by muscle mRNA and pyruvate dehydrogenase kinase 4 protein abundance changes, pointing to lack of muscle contraction per se as the primary signal for muscle adaptation.
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DOI：
10.1016/j.metabol.2009.09.014
发表时间：
2010-05
期刊：
Metabolism: clinical and experimental
影响因子：
--
作者：
Cree MG;Paddon-Jones D;Newcomer BR;Ronsen O;Aarsland A;Wolfe RR;Ferrando A
通讯作者：
Ferrando A
影响因子：
4.5
作者：
Cree MG;Newcomer BR;Herndon DN;Qian T;Sun D;Morio B;Zwetsloot JJ;Dohm GL;Fram RY;Mlcak RP;Aarsland A;Wolfe RR
通讯作者：
Wolfe RR
影响因子：
2.7
作者：
Dirks, Marlou L.;Stephens, Francis B.;Wall, Benjamin T.
通讯作者：
Wall, Benjamin T.
影响因子：
3.3
作者：
MIKINES, KJ;RICHTER, EA;GALBO, H
通讯作者：
GALBO, H
DOI：
10.1016/j.bbalip.2017.07.010
发表时间：
2017-10-01
影响因子：
4.8
作者：
Gemmink, Anne;Goodpaster, Bret H.;Hesselink, Matthijs K. C.
通讯作者：
Hesselink, Matthijs K. C.