Impaired glucose transport as a cause of decreased insulin-stimulated muscle glycogen synthesis in type 2 diabetes
Impaired glucose transport as a cause of decreased insulin-stimulated muscle glycogen synthesis in type 2 diabetes
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DOI：
10.1056/nejm199907223410404
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发表时间：
1999-07-22
影响因子：
158.5
通讯作者：
Shulman, GI
中科院分区：
文献类型：
--
作者：
Cline, GW;Petersen, KF;Shulman, GI
背景胰岛素抵抗是2型糖尿病发病机制中的一个主要因素，主要是由于胰岛素对肌肉糖原合成的刺激作用降低。虽然己糖激酶活性和葡萄糖转运已经被牵连，但肌糖原合成减少的主要速率控制步骤尚不清楚，我们使用了一种新的碳-13和磷-31核磁共振方法来测量高血糖条件下肌内葡萄糖，葡萄糖-6-磷酸和糖原浓度（血浆葡萄糖浓度，约180毫克/分升[10毫摩尔/升]）和高胰岛素血症条件下，在6例2型糖尿病患者和7例正常受试者。采用在体肌组织微透析法测定血浆葡萄糖浓度与组织间液葡萄糖浓度的梯度，开放流微灌注法测定组织间液胰岛素浓度。在血浆胰岛素浓度匹配的条件下，糖尿病患者全身葡萄糖代谢率和肌糖原合成率以及肌肉中葡萄糖-6-磷酸浓度比正常人低约80%。正常受试者的平均（+/-SD）细胞内葡萄糖浓度为2.0+/-8.2 mg/dl（0.11+/-0.46 mmol/L）。在糖尿病患者中，细胞内葡萄糖浓度为4.3+/-4.9 mg/dl（0.24+/-0.27 mmol/L），如果己糖激酶是葡萄糖代谢的速率控制酶，则该值为1/25。刺激2型糖尿病患者肌糖原合成。（N Engl J Med 1999;341：240-6.）(C)1999年，马萨诸塞州医学会。
Background Insulin resistance, a major factor in the pathogenesis of type 2 diabetes mellitus, is due mostly to decreased stimulation of glycogen synthesis in muscle by insulin. The primary rate-controlling step responsible for the decrease in muscle glycogen synthesis is not known, although hexokinase activity and glucose transport have been implicated.Methods We used a novel nuclear magnetic resonance approach with carbon-13 and phosphorus-31 to measure intramuscular glucose, glucose-6-phosphate, and glycogen concentrations under hyperglycemic conditions (plasma glucose concentration, approximately 180 mg per deciliter [10 mmol per liter]) and hyperinsulinemic conditions in six patients with type 2 diabetes and seven normal subjects. In vivo microdialysis of muscle tissue was used to determine the gradient between plasma and interstitial-fluid glucose concentrations, and open-flow microperfusion was used to determine the concentrations of insulin in interstitial fluid.Results The time course and concentration of insulin in interstitial fluid were similar in the patients with diabetes and the normal subjects. The rates of whole-body glucose metabolism and muscle glycogen synthesis and the glucose-6-phosphate concentrations in muscle were approximately 80 percent lower in the patients with diabetes than in the normal subjects under conditions of matched plasma insulin concentrations. The mean (+/-SD) intracellular glucose concentration was 2.0+/-8.2 mg per deciliter (0.11+/-0.46 mmol per liter) in the normal subjects. In the patients with diabetes, the intracellular glucose concentration was 4.3+/-4.9 mg per deciliter (0.24+/-0.27 mmol per liter), a value that was 1/25 of what it would be if hexokinase were the rate-controlling enzyme in glucose metabolism.Conclusions Impaired insulin-stimulated glucose transport is responsible for the reduced rate of insulin-stimulated muscle glycogen synthesis in patients with type 2 diabetes mellitus. (N Engl J Med 1999;341:240-6.) (C) 1999, Massachusetts Medical Society.