Rosenlund B L
Department of Clinical Biochemistry, Aker University Hospital, Oslo, Norway.
Biochem Med Metab Biol. 1993 Jun;49(3):375-91. doi: 10.1006/bmmb.1993.1038.
To investigate if alterations of the amino acid metabolism may play a more important role in the etiology of diabetic microangiopathy than hitherto recognized, free amino acids in plasma were measured by means of high-performance liquid chromatography (HPLC) in healthy individuals (REF) and patients with insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). Isoleucine and leucine in IDDM were within normal limits, whereas they were significantly higher in NIDDM (P < 0.01 and P < 0.001, respectively). This was not due to age differences. In order to evaluate the impact of insulin on amino acid metabolism, amino acids were also measured in pregnant women (PREG) undergoing glucose tolerance tests as a screening for pregnancy diabetes and in patients with polycystic ovary syndrome (PCO) undergoing euglycemic insulin clamp tests. Insulin considerably reduced the amino acid concentration. Isoleucine and leucine were particularly depressed. On the whole there was strong covariance between the three branched-chain amino acids, isoleucine, leucine, and valine (P < 0.0001). There was no covariance between amino acid and glucose or HbA1c concentrations. A protein meal strongly stimulated insulin production (+55 mIU/liter), whereas a galactose meal revealed only a minor increase in insulin response (+12 mIU/liter) in contrast to a tolerance test with the same amount of glucose (+67 mIU/liter). It is concluded that disturbed amino acid metabolism may be a more important causative factor in the etiology of diabetic microangiopathy than hitherto recognized and, in addition, that this may affect the therapeutic approach in both IDDM and NIDDM patients.
为了研究氨基酸代谢改变在糖尿病微血管病变病因中是否比迄今所认识到的发挥更重要的作用，我们采用高效液相色谱法（HPLC）测定了健康个体（REF）、胰岛素依赖型糖尿病（IDDM）患者和非胰岛素依赖型糖尿病（NIDDM）患者血浆中的游离氨基酸。IDDM患者的异亮氨酸和亮氨酸在正常范围内，而NIDDM患者的这两种氨基酸显著升高（分别为P < 0.01和P < 0.001）。这并非由于年龄差异所致。为了评估胰岛素对氨基酸代谢的影响，我们还对接受葡萄糖耐量试验以筛查妊娠糖尿病的孕妇（PREG）以及接受正常血糖胰岛素钳夹试验的多囊卵巢综合征（PCO）患者进行了氨基酸测定。胰岛素显著降低了氨基酸浓度。异亮氨酸和亮氨酸尤其受到抑制。总体而言，三种支链氨基酸异亮氨酸、亮氨酸和缬氨酸之间存在很强的协方差（P < 0.0001）。氨基酸与葡萄糖或糖化血红蛋白（HbA1c）浓度之间不存在协方差。一顿蛋白质餐强烈刺激胰岛素分泌（增加55 mIU/升），而一顿半乳糖餐与等量葡萄糖耐量试验相比，胰岛素反应仅轻微增加（增加12 mIU/升）（葡萄糖耐量试验增加67 mIU/升）。结论是，氨基酸代谢紊乱可能是糖尿病微血管病变病因中比迄今所认识到的更重要的致病因素，此外，这可能会影响IDDM和NIDDM患者的治疗方法。
