Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany.
German Center for Diabetes Research, München-Neuherberg, Germany.
JCI Insight. 2019 Nov 1;4(21):127928. doi: 10.1172/jci.insight.127928.
BACKGROUNDInsulin resistance results from impaired skeletal muscle glucose transport/phosphorylation, linked to augmented lipid availability. Despite greater intramuscular lipids, athletes are highly insulin sensitive, which could result from higher rates of insulin-stimulated glycogen synthesis or glucose transport/phosphorylation and oxidation. Thus, we examined the time course of muscle glycogen and glucose-6-phosphate concentrations during low and high systemic lipid availability.METHODSEight endurance-trained and 9 sedentary humans (VO2 peak: 56 ± 2 vs. 33 ± 2 mL/kg/min, P < 0.05) underwent 6-hour hyperinsulinemic-isoglycemic clamp tests with infusions of triglycerides or saline in a randomized crossover design. Glycogen and glucose-6-phosphate concentrations were monitored in vastus lateralis muscles using 13C/31P magnetic resonance spectroscopy.RESULTSAthletes displayed a 25% greater (P < 0.05) insulin-stimulated glucose disposal rate (Rd) than sedentary participants. During Intralipid infusion, insulin sensitivity remained higher in the athletes (ΔRd: 25 ± 3 vs. 17 ± 3 μmol/kg/min, P < 0.05), supported by higher glucose transporter type 4 protein expression than in sedentary humans. Compared to saline infusion, AUC of glucose-6-phosphate remained unchanged during Intralipid infusion in athletes (1.6 ± 0.2 mmol/L vs. 1.4 ± 0.2 [mmol/L] × h, P = n.s.) but tended to decrease by 36% in sedentary humans (1.7 ± 0.4 vs. 1.1 ± 0.1 [mmol/L] × h, P < 0.059). This drop was accompanied by a 72% higher rate of net glycogen synthesis in the athletes upon Intralipid infusion (47 ± 9 vs. 13 ± 3 μmol/kg/min, P < 0.05).CONCLUSIONAthletes feature higher skeletal muscle glucose disposal and glycogen synthesis during increased lipid availability, which primarily results from maintained insulin-stimulated glucose transport with increased myocellular glucose-6-phosphate levels for subsequent glycogen synthesis.TRIAL REGISTRATIONClinicalTrials.gov NCT01229059.FUNDINGGerman Federal Ministry of Health (BMG).
胰岛素抵抗源于骨骼肌葡萄糖转运/磷酸化受损,与脂质可用性增加有关。尽管肌肉内的脂质更多,但运动员的胰岛素敏感性很高,这可能是由于胰岛素刺激的糖原合成或葡萄糖转运/磷酸化和氧化速率更高所致。因此,我们研究了在低和高全身脂质可用性下肌肉糖原和葡萄糖-6-磷酸浓度的时程。
8 名耐力训练的人和 9 名久坐不动的人(VO2 峰值:56 ± 2 与 33 ± 2 mL/kg/min,P < 0.05)接受了 6 小时的高胰岛素高血糖钳夹试验,采用随机交叉设计输注甘油三酯或生理盐水。使用 13C/31P 磁共振波谱监测股外侧肌中的糖原和葡萄糖-6-磷酸浓度。
运动员的胰岛素刺激葡萄糖摄取率(Rd)比久坐者高 25%(P < 0.05)。在输注 Intralipid 期间,运动员的胰岛素敏感性仍然更高(ΔRd:25 ± 3 与 17 ± 3 μmol/kg/min,P < 0.05),这得益于葡萄糖转运蛋白 4 蛋白的表达高于久坐者。与输注生理盐水相比,在运动员中,葡萄糖-6-磷酸的 AUC 在输注 Intralipid 期间保持不变(1.6 ± 0.2 mmol/L 与 1.4 ± 0.2 [mmol/L] × h,P = n.s.),但在久坐者中倾向于下降 36%(1.7 ± 0.4 与 1.1 ± 0.1 [mmol/L] × h,P < 0.059)。这种下降伴随着运动员在输注 Intralipid 时净糖原合成率提高 72%(47 ± 9 与 13 ± 3 μmol/kg/min,P < 0.05)。
在脂质可用性增加的情况下,运动员的骨骼肌葡萄糖摄取和糖原合成能力更高,这主要是由于胰岛素刺激的葡萄糖转运保持不变,同时肌肉内的葡萄糖-6-磷酸水平升高,以进行随后的糖原合成。
ClinicalTrials.gov NCT01229059。
德国联邦卫生部(BMG)。