Piatti P M, Monti L D, Davis S N, Conti M, Brown M D, Pozza G, Alberti K G
Istituto Scientifico H. San Raffaele, Università di Milano, Italy.
Diabetologia. 1996 Jan;39(1):103-12. doi: 10.1007/BF00400420.
The aim of the study was to evaluate an acute decrease in NEFA levels during an oral glucose tolerance test and its effects on glucose tolerance, muscle glucose uptake and muscle indirect calorimetry in ten lean non-insulin-dependent diabetic subjects. Two 75-g oral glucose tolerance tests were performed in random order. Placebo or 250 mg acipimox (to inhibit lipolysis) were administered orally 2 h before the start of the oral glucose tolerance test. Two hours after acipimox administration (time 0), non-esterified fatty acid, glycerol and 3-hydroxybutyrate levels decreased by 84, 68 and 77% respectively, compared to basal levels. Concomitantly, muscle lipid oxidation and non-oxidative glycolysis also decreased significantly. After placebo administration, non-esterified fatty acids, glycerol and 3-hydroxybutyrate and lipid oxidation increased by 29, 28, 106 and 33%, respectively (NS vs basal levels; p < 0.001 vs acipimox). There was a negative rate of net glucose storage (interpreted as glycogenolysis) during post-absorptive conditions and at time 0 after administration of both drugs. After oral glucose tolerance test, the incremental areas of blood glucose and insulin were significantly decreased by 18 and 19% after acipimox compared to placebo. In addition, the ratio between the incremental area of forearm muscle glucose uptake and the insulin levels was significantly increased by 45% during acipimox compared to placebo administration. Glucose oxidation and non-oxidative glycolysis were significantly higher while lipid oxidation was significantly lower after acipimox than after placebo. In conclusion, our study found that in lean non-insulin-dependent diabetic subjects, an acute decrease in non-esterified fatty acid levels improves glucose tolerance, muscle glucose uptake, glucose oxidation and non-oxidative glycolysis, but is unable to normalize glucose storage.
本研究的目的是评估10名瘦型非胰岛素依赖型糖尿病患者在口服葡萄糖耐量试验期间非酯化脂肪酸（NEFA）水平的急性下降及其对葡萄糖耐量、肌肉葡萄糖摄取和肌肉间接测热法的影响。以随机顺序进行两次75克口服葡萄糖耐量试验。在口服葡萄糖耐量试验开始前2小时口服安慰剂或250毫克阿西莫司（抑制脂肪分解）。与基础水平相比，服用阿西莫司2小时后（时间0），非酯化脂肪酸、甘油和3-羟基丁酸水平分别下降了84%、68%和77%。同时，肌肉脂质氧化和非氧化糖酵解也显著下降。服用安慰剂后，非酯化脂肪酸、甘油、3-羟基丁酸和脂质氧化分别增加了29%、28%、106%和33%（与基础水平相比无统计学意义；与阿西莫司相比p<0.001）。在吸收后状态以及两种药物给药后的时间0，净葡萄糖储存率为负（解释为糖原分解）。口服葡萄糖耐量试验后，与安慰剂相比，服用阿西莫司后血糖和胰岛素的增量面积分别显著下降了18%和19%。此外，与服用安慰剂相比，服用阿西莫司期间前臂肌肉葡萄糖摄取增量面积与胰岛素水平的比值显著增加了45%。与安慰剂相比，服用阿西莫司后葡萄糖氧化和非氧化糖酵解显著更高，而脂质氧化显著更低。总之，我们的研究发现，在瘦型非胰岛素依赖型糖尿病患者中，非酯化脂肪酸水平的急性下降可改善葡萄糖耐量、肌肉葡萄糖摄取、葡萄糖氧化和非氧化糖酵解，但无法使葡萄糖储存正常化。
