Roles of glucose transport and glucose phosphorylation in muscle insulin resistance of NIDDM
Roles of glucose transport and glucose phosphorylation in muscle insulin resistance of NIDDM
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DOI：
10.2337/diabetes.45.7.915
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发表时间：
1996-07-01
期刊：
影响因子：
7.7
通讯作者：
DeFronzo, RA
中科院分区：
文献类型：
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作者：
Bonadonna, RC;DelPrato, S;DeFronzo, RA
骨骼肌葡萄糖代谢的胰岛素抵抗是NIDDM的一个关键特征。葡萄糖代谢的细胞效应在决定这种胰岛素抵抗中的定量作用仍不完全清楚。我们评估了非肥胖NIDDM患者骨骼肌的跨膜葡萄糖转运和细胞内葡萄糖磷酸化，我们在5名非肥胖NIDDM患者和7名年龄和体重匹配的对照组（研究1）中进行了正血糖胰岛素钳夹研究，结合前臂平衡技术（肱动脉和前臂深静脉插管），d -甘露醇（一种不可运输的分子），3-O-[C-14]甲基- d -葡萄糖(可运输的，同时向肱动脉注射D[3-H-3]葡萄糖（可转运和可代谢），并在深静脉流出血中测量冲洗曲线，借助前臂组织葡萄糖动力学多室模型分析冲洗曲线，确定前臂肌肉中D-葡萄糖的体内跨膜转运率和细胞内磷酸化率。在相似的稳态血浆胰岛素浓度（类似500pmol /l）和葡萄糖浓度（类似5.0 mmol/l）下，跨膜内流率（34.3 +/- 9.1 vs. 58.5 +/- 6.5 mu mol）。分钟(1)。kg(-1), P < 0.05)和细胞内磷酸化（5.4 +/- 1.6 vs . 38.8 +/- 5.1 mu mol）。分钟(1)。在NIDDM患者（研究2）中，在高血糖（类似于13 mmol/l）时重复胰岛素钳夹，试图与对照组钳夹期间测量的跨膜葡萄糖内流率相匹配，跨膜葡萄糖内流率（62 +/- 15 mu mol/l）。分钟(1)。kg(-1))与对照组相似，但细胞内葡萄糖磷酸化率(16.6 +/- 7.5 mu mol。分钟(1)。kg(-1))，虽然比研究1时的患者高3倍（P < 0.05），但仍比对照组低60% （P < 0.05）。这些数据表明，在体内评估时，葡萄糖的跨膜转运和细胞内磷酸化对胰岛素的作用都是不耐受的，并且相互作用，决定了NIDDM患者骨骼肌的胰岛素抵抗。当进行这种测量的方法可用时，将目前的结果与肌肉葡萄糖运输初始速率的体内定量进行比较将是有意义的。
Insulin resistance for glucose metabolism in skeletal muscle is a key feature in NIDDM. The quantitative role of the cellular effecters of glucose metabolism in determining this insulin resistance is still imperfectly known. We assessed transmembrane glucose transport and intracellular glucose phosphorylation in vivo in skeletal muscle in nonobese NIDDM patients, We performed euglycemic insulin clamp studies in combination with the forearm balance technique (brachial artery and deep forearm vein catheterization) in five nonobese NIDDM patients and seven age- and weight-matched control subjects (study 1), D-Mannitol (a nontransportable molecule), 3-O-[C-14]methyl-D-glucose (transportable, but not metabolizable) and D[3-H-3]glucose (transportable and metabolizable) were simultaneously injected into the brachial artery, and the washout curves were measured in the deep venous effluent blood, In vivo rates of transmembrane transport and intracellular phosphorylation of D-glucose in forearm muscle were determined by analyzing the washout curves with the aid of a multicompartmental model of glucose kinetics in forearm tissues, At similar steady-state concentrations of plasma insulin (similar to 500 pmol/l) and glucose (similar to 5.0 mmol/l), the rates of transmembrane influx (34.3 +/- 9.1 vs. 58.5 +/- 6.5 mu mol . min(-1). kg(-1), P < 0.05) and intracellular phosphorylation (5.4 +/- 1.6 vs, 38.8 +/- 5.1 mu mol . min(-1). kg(-1), P < 0.01) in skeletal muscle were markedly lower in the NIDDM patients than in the control subjects, In the NIDDM patients (study 2), the insulin clamp was repeated at hyperglycemia (similar to 13 mmol/l) trying to match the rates of transmembrane glucose influx measured during the clamp in the controls, The rate of transmembrane glucose influx (62 +/- 15 mu mol . min(-1). kg(-1)) in the NIDDM patients was similar to the control subjects, but the rate of intracellular glucose phosphorylation (16.6 +/- 7.5 mu mol . min(-1). kg(-1)), although threefold higher than in the patients during study 1 (P < 0.05), was still similar to 60% lower than in the control subjects (P < 0.05), These data suggest that when assessed in vivo, both transmembrane transport and intracellular phosphorylation of glucose are refractory to insulin action and add to each other in determining insulin resistance in skeletal muscle of NIDDM patients, It will be of interest to compare the present results with the in vivo quantitation of the initial rate of muscle glucose transport when methodology to perform this measurement becomes available.