Jucker B M, Cline G W, Barucci N, Shulman G I
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8020, USA.
Diabetes. 1999 Jan;48(1):134-40. doi: 10.2337/diabetes.48.1.134.
To examine the effects of safflower oil versus fish oil feeding on in vivo intramuscular glucose metabolism and relative pyruvate dehydrogenase (PDH) versus tricarboxylic acid (TCA) cycle flux, rats were pair-fed on diets consisting of 1) 59% safflower oil, 2) 59% menhaden fish oil, or 3) 59% carbohydrate (control) in calories. Rates of glycolysis and glycogen synthesis were assessed by monitoring [1-(13)C]glucose label incorporation into [1-(13)C]glycogen, [3-(13)C]lactate, and [3-(13)C]alanine in the hindlimb of awake rats via 13C nuclear magnetic resonance (NMR) spectroscopy during a euglycemic (approximately 6 mmol/l) hyperinsulinemic (approximately 180 microU/ml) clamp. A steady-state isotopic analysis of lactate, alanine, and glutamate was used to determine the relative PDH versus TCA cycle flux present in muscle under these conditions. The safflower oil-fed rats were insulin resistant compared with control and fish oil-fed rats, as reflected by a markedly reduced glucose infusion rate (Ginf) during the clamp (21.4 +/- 2.3 vs. 31.6 +/- 2.8 and 31.7 +/- 1.9 mg x kg(-1) x min(-1) in safflower oil versus control and fish oil groups, respectively, P < 0.006). This decrease in insulin-stimulated glucose disposal in the safflower oil group was associated with a lower rate of glycolysis (21.7 +/- 2.2 nmol x g(-1) x min(-1)) versus control (62.1 +/- 10.3 nmol x g(-1) x min(-1), P < 0.001) and versus fish oil (45.7 +/- 6.7 nmol x g(-1) x min(-1), P < 0.04), as no change in glycogen synthesis (103 +/- 15, 133 +/- 19, and 125 +/- 14 nmol x g(-1) x min(-1) in safflower oil, fish oil, and control, respectively) was detected. The intramuscular triglyceride (TG) content was increased in the safflower oil group (7.3 +/- 0.8 micromol/g) compared with the control group (5.2 +/- 0.8 micromol/g, P < 0.05) and the fish oil group (3.6 +/- 1.1 micromol/g, P < 0.01). Conversely, the percent PDH versus TCA cycle flux was decreased in the safflower oil (43 +/- 8%) versus the control (73 +/- 8%, P < 0.01) and fish oil (64 +/- 6%, P < 0.05) groups. These data suggest that the reduced insulin-stimulated glucose disposal attributed to safflower oil feeding was a consequence of reduced glycolytic flux associated with an increase in relative free fatty acid/ketone oxidation versus TCA cycle flux, whereas fish oil feeding did not alter glucose metabolism and may in part be protective of insulin-stimulated glucose disposal by limiting intramuscular TG deposition.
为研究喂食红花油与鱼油对体内肌肉葡萄糖代谢以及丙酮酸脱氢酶（PDH）与三羧酸（TCA）循环通量的影响，将大鼠按热量配对喂食以下三种饮食：1）59%红花油；2）59%鲱鱼油；3）59%碳水化合物（对照）。通过在正常血糖（约6 mmol/l）高胰岛素（约180 μU/ml）钳夹期间，利用13C核磁共振（NMR）波谱监测清醒大鼠后肢中[1-(13)C]葡萄糖标记掺入[1-(13)C]糖原、[3-(13)C]乳酸和[3-(13)C]丙氨酸的情况，评估糖酵解和糖原合成速率。采用乳酸、丙氨酸和谷氨酸的稳态同位素分析来确定在这些条件下肌肉中PDH与TCA循环通量的相对情况。与对照组和喂食鱼油的大鼠相比，喂食红花油的大鼠具有胰岛素抵抗，这在钳夹期间葡萄糖输注速率（Ginf）显著降低中得到体现（红花油组为21.4±2.3，对照组为31.6±2.8，鱼油组为31.7±1.9 mg·kg(-1)·min(-1)，P<0.006）。红花油组胰岛素刺激的葡萄糖处置减少与糖酵解速率较低有关（21.7±2.2 nmol·g(-1)·min(-1)），与对照组（62.1±10.3 nmol·g(-1)·min(-1)，P<0.001）和鱼油组（45.7±6.7 nmol·g(-1)·min(-1)，P<0.04）相比，因为未检测到糖原合成有变化（红花油组、鱼油组和对照组分别为103±15、133±19和125±14 nmol·g(-1)·min(-1)）。与对照组（5.2±0.8 μmol/g，P<0.05）和鱼油组（3.6±1.1 μmol/g，P<0.01）相比，红花油组肌肉内甘油三酯（TG）含量增加。相反，与对照组（73±8%，P<0.01）和鱼油组（64±6%，P<0.05）相比，红花油组PDH与TCA循环通量的百分比降低。这些数据表明，喂食红花油导致胰岛素刺激的葡萄糖处置减少是由于糖酵解通量降低，这与相对于TCA循环通量的游离脂肪酸/酮氧化增加有关，而喂食鱼油并未改变葡萄糖代谢，并且可能通过限制肌肉内TG沉积在一定程度上保护胰岛素刺激的葡萄糖处置。
