Localization of Rate-Limiting Defect for Glucose Disposal in Skeletal Muscle of Insulin-Resistant Type I Diabetic Patients
Localization of Rate-Limiting Defect for Glucose Disposal in Skeletal Muscle of Insulin-Resistant Type I Diabetic Patients
复制标题
胰岛素抵抗 I 型糖尿病患者骨骼肌葡萄糖处理限速缺陷的定位
作者：
H. Yki;K. Sahlin;J. Ren;V. Koivisto
我们在维持胰岛素抵抗I型（胰岛素依赖型）糖尿病患者和非糖尿病受试者前臂肌肉葡萄糖流量匹配期间，寻找肌肉葡萄糖代谢产物谱中的代谢交叉点。为了将受试者分为胰岛素敏感或胰岛素抵抗，在两种胰岛素浓度下，在血糖正常条件下测量全身和前臂葡萄糖处置、氧化和非氧化葡萄糖处置（间接量热法）和糖原合成（针刺活检中的肌糖原含量）。与对照组相比，糖尿病患者全身和前臂肌肉的葡萄糖处置显著减少。总葡萄糖处置的减少是由于氧化和非氧化葡萄糖处置的类似相对减少，指向葡萄糖代谢早期的速率限制。非氧化性葡萄糖处理的缺陷至少部分是由于肌糖原合成的缺陷，因为肌糖原含量未能响应糖尿病患者血浆胰岛素浓度的增加而增加。对大多数胰岛素抵抗的1型糖尿病患者进行了再研究，在这种情况下，通过葡萄糖的质量作用，全身葡萄糖的处置被迫与对照组相似。两组中匹配的葡萄糖流量导致前臂和全身氧化和非氧化葡萄糖处置以及肌糖原合成的速率相似，但不会导致游离细胞内葡萄糖、葡萄糖-6-磷酸、葡萄糖-1-磷酸、果糖-6-磷酸或肌肉中乳酸的积累。这些数据表明，限制速度的缺陷，葡萄糖处理的骨骼肌的I型糖尿病患者是在葡萄糖转运的水平。
We searched for metabolic crossover points in muscle glucose metabolite profiles during maintenance of matched glucose fluxes across forearm muscle in insulin-resistant type I (insulin-dependent) diabetic patients and nondiabetic subjects. To classify subjects as insulin sensitive or insulin resistant, whole-body and forearm glucose disposal, oxidative and nonoxidative glucose disposal (indirect calorimetry), and glycogen synthesis (muscle glycogen content in needle biopsies) were measured under euglycemic conditions at two insulin concentrations. Wholebody and forearm muscle glucose disposal were significantly reduced in diabetic patients compared with control subjects. The reduction in total glucose disposal was due to similar relative reductions in oxidative and nonoxidative glucose disposal, pointing toward rate limitation early in glucose metabolism. The defect in nonoxidative glucose disposal was at least partly due to a defect in muscle glycogen synthesis, because muscle glycogen content failed to increase in response to an increase in the plasma insulin concentration in the diabetic patients. The mostinsulin-resistant type 1 diabetic patients were restudied under conditions where, by glucose mass action, whole-body glucose disposal was forced to be similar to that in the control subjects. Matching glucose fluxes in the two groups resulted in similar rates of forearm and whole-body oxidative and nonoxidative glucose disposal and muscle glycogen synthesis, but it did not result in accumulation of free intracellular glucose, glucose-6-phosphate, glucose-1-phosphate, fructose-6-phosphate, or lactate in muscle. These data imply that the rate-limiting defect for glucose disposal in skeletal muscle of type I diabetic patients is at the level of glucose transport.
影响因子：
15.9
作者：
KELLEY, D;MITRAKOU, A;GERICH, J
通讯作者：
GERICH, J
影响因子：
15.9
作者：
DEFRONZO, RA;GUNNARSSON, R;WAHREN, J
通讯作者：
WAHREN, J