Luzi L, Petrides A S, De Fronzo R A
Department of Internal Medicine, University of Texas Health Science Center, San Antonio 78284.
Diabetes. 1993 Dec;42(12):1868-77. doi: 10.2337/diab.42.12.1868.
NIDDM subjects are characterized by impaired glucose tolerance and insulin resistance with respect to glucose metabolism. To examine whether the defect in glucose utilization extends to amino acid metabolism, 6 NIDDM subjects (64 +/- 4 yr of age; ideal body weight of 107 +/- 3%) and 7 control subjects (58 +/- 4 yr of age; ideal body weight of 105 +/- 2%) were studied with the euglycemic insulin clamp technique, in combination with [1-14C]leucine and indirect calorimetry. All subjects participated in two studies. In study 1, after 3 h of tracer equilibration, a 3-h insulin clamp (40 mU.m-2 x min-1) was performed to define the effect of insulin on leucine kinetics and glucose metabolism. In study 2, subjects received a repeat 3-h insulin clamp, and a balanced amino acid solution was infused to increase the plasma amino acid concentrations approximately 2-fold to examine the effect of combined physiological hyperinsulinemia-hyperaminoacidemia on the rate of leucine and glucose disposal. Insulin-mediated total body glucose uptake was significantly reduced in NIDDM during both study 1 (5.6 +/- 0.4 vs. 6.9 +/- 0.6 mg.kg-1 x min-1, P < 0.01) and study 2 (5.2 +/- 0.4 vs. 6.8 +/- 0.6, P < 0.01). Basal plasma leucine (120 +/- 10 vs. 123 +/- 11 microM) and alpha-ketoisocaproic acid concentrations (28 +/- 3 vs. 25 +/- 2 microM) were similar in NIDDM and control subjects, respectively. In contrast, the basal plasma glucose concentration (8.9 +/- 0.8 vs. 4.7 +/- 0.2 microM) and the HbA1c (8.5 +/- 0.2 vs. 5.7 +/- 0.2%) were significantly increased in NIDDM (P < 0.01). In the postabsorptive state, endogenous leucine flux, leucine oxidation, and nonoxidative leucine disposal were similar in NIDDM and control subjects. When insulin was infused without amino acids (study 1), the decrement in plasma leucine (53 +/- 5 vs. 48 +/- 4 microM), endogenous leucine flux (13 +/- 2 vs. 11 +/- 1 mumol.m-2 x min-1), leucine oxidation (1.6 +/- 0.2 vs. 1.3 +/- 0.1 mumol.m-2 x min-1), and nonoxidative leucine disposal (10 +/- 1 vs. 8 +/- 1 mumol.m-2 x min-1) was comparable in both groups. During combined insulin and amino acid infusion (study 2), plasma leucine concentration (185 +/- 20 vs. 190 +/- 15 microM) rose similarly in NIDDM and control subjects.(ABSTRACT TRUNCATED AT 400 WORDS)
非胰岛素依赖型糖尿病（NIDDM）患者的特征是葡萄糖耐量受损以及在葡萄糖代谢方面存在胰岛素抵抗。为了研究葡萄糖利用缺陷是否扩展至氨基酸代谢，我们使用正常血糖胰岛素钳夹技术，并结合[1-14C]亮氨酸和间接测热法，对6名NIDDM患者（年龄64±4岁；理想体重为107±3%）和7名对照者（年龄58±4岁；理想体重为105±2%）进行了研究。所有受试者均参与了两项研究。在研究1中，经过3小时的示踪剂平衡后，进行了3小时的胰岛素钳夹（40 mU·m-2·min-1），以确定胰岛素对亮氨酸动力学和葡萄糖代谢的影响。在研究2中，受试者接受重复的3小时胰岛素钳夹，并输注平衡氨基酸溶液以使血浆氨基酸浓度增加约2倍（ABSTRACT TRUNCATED AT 400 WORDS），以研究生理性高胰岛素血症-高氨基酸血症联合作用对亮氨酸和葡萄糖处置率的影响。在研究1（5.6±0.4对6.9±0.6 mg·kg-1·min-1，P<0.01）和研究2（5.2±0.4对6.8±0.6，P<0.01）期间，NIDDM患者中胰岛素介导的全身葡萄糖摄取均显著降低。NIDDM患者和对照者的基础血浆亮氨酸（120±10对123±11 μM）和α-酮异己酸浓度（28±3对25±2 μM）分别相似。相比之下，NIDDM患者的基础血浆葡萄糖浓度（8.9±0.8对4.7±0.2 μM）和糖化血红蛋白（HbA1c）（8.5±0.2对5.
