Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes
Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes
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DOI：
10.1056/nejmoa031314
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发表时间：
2004-02-12
影响因子：
158.5
通讯作者：
Shulman, GI
中科院分区：
文献类型：
--
作者：
Petersen, KF;Dufour, S;Shulman, GI
背景资料：胰岛素抵抗似乎是2型糖尿病患者子女发生糖尿病的最佳预测因素，但其机制尚不清楚。我们对健康、年轻、瘦、肥胖、肥胖和肥胖的人进行了高胰岛素-正葡萄糖钳夹研究，2型糖尿病患者和胰岛素敏感对照受试者的胰岛素抵抗后代在年龄、身高、体重和体力活动方面相匹配，以评估肝脏和肌肉对胰岛素的敏感性。质子（（sup 1）H）磁共振波谱研究进行测量肌细胞内脂质和肝内甘油三酯含量。通过测量[（sup 2）H（sub 5）]甘油周转率并结合皮下脂肪甘油释放的微透析测量，评估全身和皮下脂肪脂解率。结果：胰岛素抵抗组受胰岛素刺激的肌肉葡萄糖摄取率比胰岛素敏感组低约60%（P < 0.05），胰岛素抵抗组受胰岛素刺激的肌肉葡萄糖摄取率比胰岛素敏感组低约60%（P < 0.05）。
Background: Insulin resistance appears to be the best predictor of the development of diabetes in the children of patients with type 2 diabetes, but the mechanism responsible is unknown.Methods: We performed hyperinsulinemic-euglycemic clamp studies in combination with infusions of [6,6-(sup 2)H(sub 2)]glucose in healthy, young, lean, insulin-resistant offspring of patients with type 2 diabetes and insulin-sensitive control subjects matched for age, height, weight, and physical activity to assess the sensitivity of liver and muscle to insulin. Proton ((sup 1)H) magnetic resonance spectroscopy studies were performed to measure intramyocellular lipid and intrahepatic triglyceride content. Rates of whole-body and subcutaneous fat lipolysis were assessed by measuring the rates of [(sup 2)H(sub 5)]glycerol turnover in combination with microdialysis measurements of glycerol release from subcutaneous fat. We performed (sup 31)P magnetic resonance spectroscopy studies to assess the rates of mitochondrial oxidative-phosphorylation activity in muscle.Results: The insulin-stimulated rate of glucose uptake by muscle was approximately 60 percent lower in the insulin-resistant subjects than in the insulin-sensitive control subjects (P