Zierath J R, He L, Gumà A, Odegoard Wahlström E, Klip A, Wallberg-Henriksson H
Department of Clinical Physiology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
Diabetologia. 1996 Oct;39(10):1180-9. doi: 10.1007/BF02658504.
We investigated the response of the glucose transport system to insulin, in the presence of ambient glucose concentrations, in isolated skeletal muscle from seven patients with non-insulin-dependent diabetes mellitus (NIDDM) (age, 55 +/- 3 years, BMI 27.4 +/- 1.8 kg/m2) and seven healthy control subjects (age, 54 +/- 3 years, BMI 26.5 +/- 1.1 kg/m2). Insulin-mediated whole body glucose utilization was similar between the groups when studied in the presence of ambient glucose concentrations (approximately 10 mmol/l for the NIDDM patients and 5 mmol/l for the control subjects). Samples were obtained from the vastus lateralis muscle, by means of an open muscle biopsy procedure, before and after a 40-min insulin infusion. An increase in serum insulin levels from 54 +/- 12 to 588 +/- 42 pmol/l, induced a 1.6 +/- 0.2-fold increase in glucose transporter protein (GLUT4) in skeletal muscle plasma membranes obtained from the control subjects (p < 0.05), whereas no significant increase was noted in plasma membrane fractions prepared from NIDDM muscles, despite a similar increase in serum insulin levels. At concentrations of 5 mmol/l 3-O-methylglucose in vitro, insulin (600 pmol/l) induced a 2.2-fold (p < 0.05) increase in glucose transport in NIDDM muscles and a 3.4-fold (p < 0.001) increase in the control muscles. Insulin-stimulated 3-O-methylglucose transport was positively correlated with whole body insulin-mediated glucose uptake in all participants (r = 0.78, p < 0.001) and negatively correlated with fasting plasma glucose levels in the NIDDM subjects (r = 0.93, p < 0.001). Muscle fibre type distribution and capillarization were similar between the groups. Our results suggest that insulin-stimulated glucose transport in skeletal muscle from patients with NIDDM is down-regulated in the presence of hyperglycaemia. The increased flux of glucose as a consequence of hyperglycaemia may result in resistance to any further insulin-induced gain of GLUT4 at the level of the plasma membrane.
我们研究了在环境葡萄糖浓度存在的情况下，非胰岛素依赖型糖尿病（NIDDM）患者（7例，年龄55±3岁，体重指数27.4±1.8kg/m²）和7名健康对照者（年龄54±3岁，体重指数26.5±1.1kg/m²）的分离骨骼肌中葡萄糖转运系统对胰岛素的反应。在环境葡萄糖浓度（NIDDM患者约为10mmol/L，对照者约为5mmol/L）下进行研究时，两组之间胰岛素介导的全身葡萄糖利用率相似。通过开放式肌肉活检程序，在40分钟胰岛素输注前后，从股外侧肌获取样本。对照者血清胰岛素水平从54±12pmol/L升至588±42pmol/L，导致骨骼肌质膜中葡萄糖转运蛋白（GLUT4）增加1.6±0.2倍（p<0.05），而尽管血清胰岛素水平有类似升高，但NIDDM肌肉制备的质膜部分未观察到显著增加。在体外3 - O - 甲基葡萄糖浓度为5mmol/L时，胰岛素（600pmol/L）使NIDDM肌肉中的葡萄糖转运增加2.2倍（p<0.05），对照肌肉中增加3.4倍（p<0.001）。胰岛素刺激的3 - O - 甲基葡萄糖转运在所有参与者中与全身胰岛素介导的葡萄糖摄取呈正相关（r = 0.78，p<0.001），在NIDDM受试者中与空腹血糖水平呈负相关（r = 0.93，p<0.001）。两组之间肌纤维类型分布和毛细血管化相似。我们的结果表明，在高血糖情况下，NIDDM患者骨骼肌中胰岛素刺激的葡萄糖转运下调。高血糖导致的葡萄糖通量增加可能导致在质膜水平对胰岛素诱导的GLUT4进一步增加产生抵抗。
