Turpeinen A K, Takala T O, Nuutila P, Axelin T, Luotolahti M, Haaparanta M, Bergman J, Hämäläinen H, Iida H, Mäki M, Uusitupa M I, Knuuti J
Department of Clinical Nutrition, University of Kuopio and Kuopio University Hospital, Finland.
Diabetes. 1999 Jun;48(6):1245-50. doi: 10.2337/diabetes.48.6.1245.
Free fatty acids (FFAs) are an important substrate for myocardial and skeletal muscle metabolism, and increased availability and oxidation of FFA are suggested to be associated with insulin resistance. This study was undertaken to assess whether myocardial or muscle uptake of FFA is altered in patients with impaired glucose tolerance (IGT). Eight healthy men (control group; age 48+/-1 years, BMI 25+/-1 kg/m2, mean +/- SE) and eight men with IGT (glucose-intolerant group; age 49+/-1 years, BMI 29+/-1 kg/m2) were studied in the fasting state. Myocardial oxygen consumption and blood flow and myocardial and femoral muscle FFA uptake rates were measured with positron emission tomography (PET) and [15O]O2, [15O]H2O, [15O]CO, and 14(R, S)-[18F]fluoro-6-thia-heptadecanoic acid ([18F]FTHA), a fatty acid tracer trapped into the cell after undergoing initial steps of beta-oxidation. Serum glucose and insulin concentrations were higher in the glucose-intolerant group during the PET study, but FFA concentrations were comparable between the groups. No differences between the groups were observed in the myocardial blood flow, oxygen consumption, fractional FTHA uptake rates, or FFA uptake indices (5.6+/-0.4 vs. 5.2+/-0.4 pmol x 100 g(-1) x min(-1), glucose-intolerant versus control, NS). In the femoral muscle, fractional FTHA uptake (0.0062+/-0.0003 vs. 0.0072+/-0.0003 min(-1), P = 0.044) and FFA uptake indices (0.30+/-0.02 vs. 0.43+/-0.04 min(-1), P = 0.020) were significantly lower in the glucose-intolerant group than in the control group. In conclusion, when studied at the fasting state and normal serum FFA concentrations, subjects with IGT have similar myocardial but lowered femoral muscle FFA uptake. This finding argues against the hypothesis that an increased oxidation of serum FFA, via the competition of glucose and FFA as fuel sources, is the primary cause for impaired peripheral glucose utilization and insulin resistance commonly observed in IGT.
游离脂肪酸（FFAs）是心肌和骨骼肌代谢的重要底物，FFA可用性和氧化增加被认为与胰岛素抵抗有关。本研究旨在评估糖耐量受损（IGT）患者的心肌或肌肉对FFA的摄取是否发生改变。对8名健康男性（对照组；年龄48±1岁，体重指数25±1kg/m²，均值±标准误）和8名IGT男性（糖耐量不耐受组；年龄49±1岁，体重指数29±1kg/m²）进行空腹状态研究。采用正电子发射断层扫描（PET）以及[15O]O2、[15O]H2O、[15O]CO和14（R，S）-[18F]氟-6-硫代十七烷酸（[18F]FTHA，一种在经历β-氧化初始步骤后被困在细胞内的脂肪酸示踪剂）测量心肌耗氧量、血流量以及心肌和股四头肌FFA摄取率。PET研究期间，糖耐量不耐受组的血清葡萄糖和胰岛素浓度较高，但两组间FFA浓度相当。两组在心肌血流量、耗氧量、FTHA摄取分数率或FFA摄取指数方面未观察到差异（糖耐量不耐受组与对照组分别为5.6±0.4 vs. 5.2±0.4 pmol×100g⁻¹×min⁻¹，无显著性差异）。在股四头肌中，糖耐量不耐受组的FTHA摄取分数（0.0062±0.0003 vs. 0.0072±0.0003 min⁻¹，P = 0.044）和FFA摄取指数（0.30±0.02 vs. 0.43±0.04 min⁻¹，P = 0.020）显著低于对照组。总之，在空腹状态和正常血清FFA浓度下进行研究时，IGT受试者的心肌FFA摄取相似，但股四头肌FFA摄取降低。这一发现与以下假设相悖，即通过葡萄糖和FFA作为燃料来源的竞争，血清FFA氧化增加是IGT中常见的外周葡萄糖利用受损和胰岛素抵抗的主要原因。
