Kusunoki M, Cooney G J, Hara T, Storlien L H
First Department of Internal Medicine, Aichi Medical University, Nagoya, Japan.
Diabetes. 1995 Jun;44(6):718-20. doi: 10.2337/diab.44.6.718.
Fat feeding produces whole-body insulin resistance and decreased glucose uptake in muscle tissue of rats. To examine the effect of glucocorticoid blockade on the insulin resistance caused by high-fat feeding, four groups of rats were fed diets high in starch (70% of calories) or fat (59% of calories) for 4 weeks with or without the antiglucocorticoid RU486 (69.8 mumol.kg-1.day-1) in the food. Whole-body insulin action was assessed by the euglycemic clamp technique at an upper physiological insulin level with bolus 2-[3H]deoxyglucose to determine individual tissue insulin-stimulated glucose uptake. Whole-body glucose utilization (clamp glucose infusion rate [GIR]) was decreased by high-fat feeding (GIR 68.3 +/- 12.2 vs. 182.6 +/- 12.8 mumol.kg-1.min-1 for the starch-fed group; P < 0.001). Addition of RU486 to the diet significantly improved (GIR 133.9 +/- 12.8 mumol.kg-1.min-1; P < 0.01), but did not fully reverse, the insulin resistance caused by fat feeding. RU486 was without effect in the starch-fed rats. In skeletal muscles, RU486 ameliorated 62 and 68% of the insulin resistance produced by fat feeding in red quadriceps and extensor digitorum longus hindlimb muscles, respectively, but had no effect in heart or white adipose tissue. These results suggest that glucocorticoids play, in a tissue-specific manner, a role in the maintenance and/or production of insulin resistance produced by high-fat feeding.
喂食脂肪会导致大鼠全身胰岛素抵抗，并降低肌肉组织对葡萄糖的摄取。为了研究糖皮质激素阻断对高脂喂养所致胰岛素抵抗的影响，将四组大鼠分别喂食高淀粉（热量的70%）或高脂肪（热量的59%）饮食4周，饮食中添加或不添加抗糖皮质激素RU486（69.8 μmol·kg⁻¹·d⁻¹）。采用正常血糖钳夹技术，在生理胰岛素水平上限，通过静脉推注2-[³H]脱氧葡萄糖来评估全身胰岛素作用，以确定各个组织胰岛素刺激的葡萄糖摄取。高脂喂养会降低全身葡萄糖利用率（钳夹葡萄糖输注速率[GIR]）（淀粉喂养组的GIR为68.3±12.2 vs. 182.6±12.8 μmol·kg⁻¹·min⁻¹；P<0.001）。饮食中添加RU486可显著改善（GIR为133.9±12.8 μmol·kg⁻¹·min⁻¹；P<0.01）但不能完全逆转高脂喂养所致的胰岛素抵抗。RU486对淀粉喂养的大鼠没有影响。在骨骼肌中，RU486分别改善了红色股四头肌和后肢趾长伸肌中高脂喂养所致胰岛素抵抗的62%和68%，但对心脏或白色脂肪组织没有影响。这些结果表明，糖皮质激素以组织特异性方式在高脂喂养所致胰岛素抵抗的维持和/或产生中起作用。
