Limitations to basal and insulin-stimulated skeletal muscle glucose uptake in the high-fat-fed rat
Limitations to basal and insulin-stimulated skeletal muscle glucose uptake in the high-fat-fed rat
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DOI：
10.1152/ajpendo.2000.279.5.e1064
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发表时间：
2000-11-01
影响因子：
5.1
通讯作者：
Wasserman, DH
中科院分区：
文献类型：
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作者：
Halseth, AE;Bracy, DP;Wasserman, DH
喂食高脂肪食物的大鼠表现出胰岛素刺激的骨骼肌葡萄糖摄取迟钝。目前尚不清楚这是否仅仅是由于葡萄糖转运缺陷，还是葡萄糖转运和磷酸化也受损。为了确定这一点，给大鼠喂食标准食物（对照大鼠）或高脂肪饮食（HF大鼠）4周。然后在基础条件下或在高胰岛素正常血糖钳夹期间对有意识的大鼠进行实验。大鼠连续灌注3- o -甲基-[H-3]葡萄糖（3-O-MG）和[1-C-14]甘露醇。用总肌葡萄糖浓度和胞内与胞外3-O-MG浓度的稳态比值[其分布基于经肌层葡萄糖梯度（TSGG）]计算比目鱼肌层内外表面（分别为[G]（im）和[G](om)）的葡萄糖浓度。在两个快速收缩肌肉中也测量了总肌肉葡萄糖。心衰大鼠肌肉葡萄糖摄取明显减少。在对照大鼠中，高胰岛素血症导致比目鱼肌TSGG与基础相比下降，原因是升高[G]（im）。在高胰岛素血症的HF大鼠中，[G]（im）也超过零。高胰岛素血症也降低了HF大鼠的肌肉葡萄糖，暗示葡萄糖输送受损。总之，细胞外和细胞内肌肉葡萄糖摄取成分的缺陷在胰岛素抵抗模型中具有重要的功能意义。
Rats fed a high-fat diet display blunted insulin-stimulated skeletal muscle glucose uptake. It is not clear whether this is due solely to a defect in glucose transport, or if glucose delivery and phosphorylation are also impaired. To determine this, rats were fed standard chow (control rats) or a high-fat diet (HF rats) for 4 wk. Experiments were then performed on conscious rats under basal conditions or during hyperinsulinemic euglycemic clamps. Rats received primed constant infusions of 3-O-methyl-[H-3] glucose (3-O-MG) and [1-C-14]mannitol. Total muscle glucose concentration and the steady-state ratio of intracellular to extracellular 3-O-MG concentration [which distributes based on the transsarcolemmal glucose gradient (TSGG)] were used to calculate glucose concentrations at the inner and outer sarcolemmal surfaces ([G](im) and [G](om), respectively) in soleus. Total muscle glucose was also measured in two fast-twitch muscles. Muscle glucose uptake was markedly decreased in HF rats. In control rats, hyperinsulinemia resulted in a decrease in soleus TSGG compared with basal, due to increased [G](im). In HF rats during hyperinsulinemia, [G](im) also exceeded zero. Hyperinsulinemia also decreased muscle glucose in HF rats, implicating impaired glucose delivery. In conclusion, defects in extracellular and intracellular components of muscle glucose uptake are of major functional significance in this model of insulin resistance.