Department of Human Biology, NUTRIM School for Nutrition, Toxicology, and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
Diabetes. 2012 Oct;61(10):2472-8. doi: 10.2337/db11-1832. Epub 2012 Jul 10.
Fat accumulation in skeletal muscle combined with low mitochondrial oxidative capacity is associated with insulin resistance (IR). Endurance-trained athletes, characterized by a high oxidative capacity, have elevated intramyocellular lipids, yet are highly insulin sensitive. We tested the hypothesis that a high oxidative capacity could attenuate lipid-induced IR. Nine endurance-trained (age = 23.4 ± 0.9 years; BMI = 21.2 ± 0.6 kg/m(2)) and 10 untrained subjects (age = 21.9 ± 0.9 years; BMI = 22.8 ± 0.6 kg/m(2)) were included and underwent a clamp with either infusion of glycerol or intralipid. Muscle biopsies were taken to perform high-resolution respirometry and protein phosphorylation/expression. Trained subjects had ~32% higher mitochondrial capacity and ~22% higher insulin sensitivity (P < 0.05 for both). Lipid infusion reduced insulin-stimulated glucose uptake by 63% in untrained subjects (P < 0.05), whereas this effect was blunted in trained subjects (29%, P < 0.05). In untrained subjects, lipid infusion reduced oxidative and nonoxidative glucose disposal (NOGD), whereas trained subjects were completely protected against lipid-induced reduction in NOGD, supported by dephosphorylation of glycogen synthase. We conclude that chronic exercise training attenuates lipid-induced IR and specifically attenuates the lipid-induced reduction in NOGD. Signaling data support the notion that high glucose uptake in trained subjects is maintained by shuttling glucose toward storage as glycogen.
骨骼肌脂肪堆积加上低线粒体氧化能力与胰岛素抵抗（IR）有关。具有高氧化能力的耐力训练运动员，其细胞内脂质含量升高，但对胰岛素非常敏感。我们检验了一个假设，即高氧化能力可以减轻脂质引起的 IR。共纳入 9 名耐力训练运动员（年龄=23.4±0.9 岁；BMI=21.2±0.6kg/m²）和 10 名未经训练的受试者（年龄=21.9±0.9 岁；BMI=22.8±0.6kg/m²），并进行了甘油或脂肪乳剂输注的钳夹试验。采集肌肉活检标本进行高分辨率呼吸测定和蛋白质磷酸化/表达。训练有素的受试者的线粒体容量高约 32%，胰岛素敏感性高约 22%（两者均 P<0.05）。脂肪乳剂输注使未经训练的受试者胰岛素刺激的葡萄糖摄取减少了 63%（P<0.05），而这种作用在训练有素的受试者中被削弱（减少 29%，P<0.05）。在未经训练的受试者中，脂肪乳剂输注降低了氧化和非氧化葡萄糖处置（NOGD），而训练有素的受试者完全免受脂质诱导的 NOGD 降低的影响，这得益于糖原合酶的去磷酸化。我们得出结论，慢性运动训练可减轻脂质引起的 IR，特别是可减轻脂质引起的 NOGD 降低。信号数据支持这样一种观点，即训练有素的受试者的高葡萄糖摄取是通过将葡萄糖转移到糖原储存来维持的。
