Denne S C, Brechtel G, Johnson A, Liechty E A, Baron A D
Department of Pediatrics, Indiana University Medical Center, Indianapolis, USA.
J Clin Endocrinol Metab. 1995 Aug;80(8):2371-7. doi: 10.1210/jcem.80.8.7629232.
To assess how noninsulin-dependent diabetes mellitus (NIDDM) and diabetes control may alter whole body and skeletal muscle proteolysis, we measured the rate of appearance (Ra) of phenylalanine (reflecting proteolysis) in the whole body and across the leg (reflecting skeletal muscle), using a constant tracer infusion of [2H5]phenylalanine in the basal state and during high-dose euglycemic hyperinsulinemia in 6 NIDDM and 10 control subjects. Studies were performed in NIDDM subjects 2 weeks after complete withdrawal of antidiabetic treatment and again after intensive insulin therapy. After intensive treatment, significant reductions were measured in hemoglobin A1C, fasting glucose concentrations, and basal hepatic glucose output. In contrast, there was no change after therapy in basal whole body or leg phenylalanine Ra. Compared with that of controls, whole body phenylalanine Ra was significantly higher and leg phenylalanine Ra significantly lower in NIDDM subjects. During euglycemic hyperinsulinemia, whole body phenylalanine Ra was significantly suppressed (approximately 15%) below basal values before and after therapy in NIDDM subjects and similarly suppressed in control subjects. However, in NIDDM subjects, euglycemic hyperinsulinemia did not reduce leg phenylalanine Ra below basal values either before or after therapy, whereas hyperinsulinemia resulted in a 42% suppression of leg phenylalanine Ra in controls. We conclude that 1) the clear improvement in glucose metabolism produced by intensive insulin therapy in NIDDM is not accompanied by changes in whole body or skeletal muscle proteolysis; 2) skeletal muscle proteolysis is reduced even though whole body proteolysis is increased in NIDDM subjects compared with controls; and 3) although a high-dose systemic infusion of insulin significantly reduces whole body proteolysis in both NIDDM and control subjects, skeletal muscle proteolysis is suppressed only in controls. We speculate that in NIDDM, high basal insulin concentrations (approximately 200 pmol/L, unaltered by therapy) maximally suppress skeletal muscle proteolysis, and therefore higher insulin concentrations produce no additional suppression in skeletal muscle.
为了评估非胰岛素依赖型糖尿病（NIDDM）及糖尿病控制情况如何改变全身和骨骼肌蛋白水解，我们在6名NIDDM患者和10名对照受试者的基础状态及高剂量正常血糖高胰岛素血症期间，通过持续输注[2H5]苯丙氨酸示踪剂，测量了全身和腿部（反映骨骼肌）苯丙氨酸的出现率（Ra，反映蛋白水解）。研究在NIDDM患者完全停用抗糖尿病治疗2周后进行，强化胰岛素治疗后再次进行。强化治疗后，糖化血红蛋白A1C、空腹血糖浓度和基础肝葡萄糖输出量均显著降低。相比之下，治疗后基础全身或腿部苯丙氨酸Ra没有变化。与对照组相比，NIDDM患者全身苯丙氨酸Ra显著更高，而腿部苯丙氨酸Ra显著更低。在正常血糖高胰岛素血症期间，NIDDM患者治疗前后全身苯丙氨酸Ra均显著低于基础值（约15%），对照组也有类似程度的降低。然而，在NIDDM患者中，正常血糖高胰岛素血症在治疗前后均未使腿部苯丙氨酸Ra降至基础值以下，而高胰岛素血症使对照组腿部苯丙氨酸Ra降低了42%。我们得出结论：1）NIDDM患者强化胰岛素治疗使葡萄糖代谢明显改善，但全身或骨骼肌蛋白水解没有变化；2）与对照组相比，NIDDM患者全身蛋白水解增加，但骨骼肌蛋白水解减少；3）尽管高剂量全身输注胰岛素可显著降低NIDDM患者和对照受试者的全身蛋白水解，但仅在对照组中抑制了骨骼肌蛋白水解。我们推测，在NIDDM中，高基础胰岛素浓度（约200 pmol/L，治疗后未改变）最大程度地抑制了骨骼肌蛋白水解，因此更高的胰岛素浓度不会对骨骼肌产生额外抑制。
