INTERACTION BETWEEN GLUCOSE AND FREE FATTY-ACID METABOLISM IN HUMAN SKELETAL-MUSCLE
INTERACTION BETWEEN GLUCOSE AND FREE FATTY-ACID METABOLISM IN HUMAN SKELETAL-MUSCLE
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DOI：
10.1172/jci116603
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发表时间：
1993-07-01
影响因子：
15.9
通讯作者：
MANDARINO, LJ
中科院分区：
文献类型：
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作者：
KELLEY, DE;MOKAN, M;MANDARINO, LJ
FFA代谢抑制正常人细胞内胰岛素介导的肌肉葡萄糖代谢的机制尚不清楚。我们使用腿部平衡技术和肌肉活检来确定高胰岛素血症期间FFA的实验性维持如何改变肌肉葡萄糖摄取、氧化、糖酵解、储存、丙酮酸脱氢酶（PDH）或糖原合酶（GS）。10名健康志愿者进行了两次正常血糖胰岛素钳夹实验。在一种情况下，通过脂肪乳剂输注维持FFA;在另一种情况下。FFA被允许下降。用[9，10-H-3]棕榈酸盐监测腿部FFA摄取。在高胰岛素血症期间维持FFA可降低肌肉葡萄糖摄取（1.57+/-0.31 vs 2. 44 +/-0.39 mumol/min/100 ml组织，P < 0.01），腿部呼吸商（0.86 ± 0.02 vs 0.93 ± 0.02，P < 0.05），葡萄糖对腿部耗氧量的贡献（53+/-6vs76 +/-8%，P < 0.05）和PDH活性（0.328+/-0.053vs0.662 +/-0.176nmol/min/mg，P < 0.05）。腿部乳酸平衡增加。FFA替代的最大影响是减少肌肉葡萄糖储存（0.36+/-0.20 vs 1. 24 +/-0.25 mumol/min/100 ml，P < 0.01），同时伴有GS流速分数降低（0.129+/-0.26 vs 0. 169 +/-0.033，P < 0.01）。这些结果证实在人骨骼肌中存在葡萄糖和FFA作为氧化燃料之间的竞争，通过抑制PDH介导。高胰岛素血症期间FFA水平的维持最显著地抑制了腿部肌肉葡萄糖储存，伴随着GS活性的降低。
The mechanism by which FFA metabolism inhibits intracellular insulin-mediated muscle glucose metabolism in normal humans is unknown. We used the leg balance technique with muscle biopsies to determine how experimental maintenance of FFA during hyperinsulinemia alters muscle glucose uptake, oxidation, glycolysis, storage, pyruvate dehydrogenase (PDH), or glycogen synthase (GS). 10 healthy volunteers had two euglycemic insulin clamp experiments. On one occasion, FFA were maintained by lipid emulsion infusion; on the other. FFA were allowed to fall. Leg FFA uptake was monitored with [9,10-H-3]palmitate.Maintenance of FFA during hyperinsulinemia decreased muscle glucose uptake (1.57+/-0.31 vs 2.44+/-0.39 mumol/min per 100 ml tissue, P < 0.01), leg respiratory quotient (0.86+/-0.02 vs 0.93+/-0.02, P < 0.05), contribution of glucose to leg oxygen consumption (53+/-6 vs 76+/-8%, P < 0.05), and PDH activity (0.328+/-0.053 vs 0.662+/-0.176 nmol/min per mg, P < 0.05). Leg lactate balance was increased. The greatest effect of FFA replacement was reduced muscle glucose storage (0.36+/-0.20 vs 1.24+/-0.25 mumol/min per 100 ml, P < 0.01 ), accompanied by decreased GS fractional velocity (0.129+/-0.26 vs 0.169+/-0.033, P < 0.01). These results confirm in human skeletal muscle the existence of competition between glucose and FFA as oxidative fuels, mediated by suppression of PDH. Maintenance of FFA levels during hyperinsulinemia most strikingly inhibited leg muscle glucose storage, accompanied by decreased GS activity.