QUANTITATION OF MUSCLE GLYCOGEN-SYNTHESIS IN NORMAL SUBJECTS AND SUBJECTS WITH NON-INSULIN-DEPENDENT DIABETES BY C-13 NUCLEAR MAGNETIC-RESONANCE SPECTROSCOPY
QUANTITATION OF MUSCLE GLYCOGEN-SYNTHESIS IN NORMAL SUBJECTS AND SUBJECTS WITH NON-INSULIN-DEPENDENT DIABETES BY C-13 NUCLEAR MAGNETIC-RESONANCE SPECTROSCOPY
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DOI：
10.1056/nejm199001253220403
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发表时间：
1990-01-25
影响因子：
158.5
通讯作者：
SHULMAN, RG
中科院分区：
文献类型：
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作者：
SHULMAN, GI;ROTHMAN, DL;SHULMAN, RG
为了检查非胰岛素依赖型糖尿病 (NIDDM) 受试者的胰岛素作用缺陷在多大程度上可以由肌糖原合成受损来解释，我们对 5 名 NIDDM 受试者和 6 名年龄和体重匹配的健康受试者进行了使用 [13C] 葡萄糖的联合高血糖-高胰岛素钳夹研究。通过具有 15.5 分钟时间分辨率和 13C 表面线圈的核磁共振 (NMR) 波谱仪直接在腓肠肌中测量静脉输注的 [1-13C] 葡萄糖掺入肌糖原的速率。两个研究组中胰岛素（约 400 pmol/L）和葡萄糖（约 10 mmol/L）的稳态血浆浓度相似。通过13C NMR测定，糖原合成的平均(.±.SE)速率为78.±.SE。 28 和 183 .+-。糖尿病受试者和正常受试者每分钟每千克肌肉组织（湿重）分别为 39 μmol-葡萄糖基单位（P < 0.05）。与正常受试者(51±3μmol每千克每分钟；P<0.005)相比，糖尿病患者的平均葡萄糖摄取显着降低(30±4μmol每千克每分钟)。非氧化性葡萄糖代谢的平均速率为22.+-。糖尿病受试者为每公斤每分钟 4.mu.mol，而糖尿病受试者为每公斤 4.+-。正常受试者每公斤每分钟 4 .mu.mol (P < 0.005)。当这些速率外推到适用于整个身体时，肌糖原的合成将占正常和糖尿病受试者全身葡萄糖摄取和所有非氧化葡萄糖代谢的大部分。我们得出的结论是，肌糖原合成是正常和糖尿病受试者葡萄糖处理的主要途径，并且肌糖原合成缺陷在 NIDDM 患者发生的胰岛素抵抗中起主导作用。
To examine the extent to which the defect in insulin action in subjects with non-insulin-dependent diabetes mellitus (NIDDM) can be accounted for by impairment of muscle glycogen synthesis, we peroformed combined hyperglycemic-hyperinsulinemic clamp studies with [13C]glucose in five subjects with NIDDM and in six age- and weight-matched healthy subjects. The rate of incorporation of intravenously infused [1-13C]glucose into muscle glycogen was measured directly in the gastrocnemius muscle by means of a nuclear magnetic resonance (NMR) spectrometer with a 15.5-minute time resolution and a 13C surface coil. The steady-state plasma concentrations of insulin (.apprxeq. 400 pmol per liter) and glucose (.apprxeq. 10 mmol per liter) were similar in both study groups. The mean (.+-. SE) rate of glycogen synthesis, as determined by 13C NMR, was 78 .+-. 28 and 183 .+-. 39 .mu.mol-glucosyl units per kilogram of muscle tissue (wet weight) per minute in the diabetic and normal subjects, respectively (P < 0.05). The mean glucose uptake was markedly reduced in the diabetic (30 .+-. 4 .mu.mol per kilogram per minute) as compared with the normal subjects (51 .+-. 3 .mu.mol per kilogram per minute; P < 0.005). The mean rate of nonoxidative glucose metabolism was 22 .+-. 4 .mu.mol per kilogram per minute in the diabetic subjects and 42 .+-. 4 .mu.mol per kilogram per minute in the normal subjects (P < 0.005). When these rates are extrapolated to apply to the whole body, the synthesis of muscle glycogen would account for most of the total-body glucose uptake and all of the nonoxidative glucose metabolism in both normal and diabetic subjects. We conclude that muscle glycogen synthesis is the principal pathway of glucose disposal in both normal and diabetic subjects and that defects in muscle glycogen synthesis have a dominant role in the insulin resistance that occurs in persons with NIDDM.