AMP-activated protein kinase (AMPK) is activated in muscle of subjects with type 2 diabetes during exercise
AMP-activated protein kinase (AMPK) is activated in muscle of subjects with type 2 diabetes during exercise
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DOI：
10.2337/diabetes.50.5.921
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发表时间：
2001-05-01
期刊：
影响因子：
7.7
通讯作者：
Goodyear, LJ
中科院分区：
文献类型：
--
作者：
Musi, N;Fujii, N;Goodyear, LJ
2型糖尿病患者胰岛素刺激的GLUT 4易位受损相反，运动导致这些患者的GLUT 4易位和葡萄糖摄取正常增加。最近有几个研究小组假设，运动通过AMP活化蛋白激酶（AMPK）激活介导的胰岛素非依赖性机制增加葡萄糖摄取。如果这一假设是正确的，2型糖尿病患者在运动时应该有正常的AMPK激活。7例2型糖尿病患者和8例对照组受试者在自行车测力计上以10%的最大工作负荷进行45分钟的运动。在运动前、运动后20和45 min以及运动后30 min分别取股外侧肌活检。运动45分钟后，糖尿病组的血糖浓度从7.6 mmol/l降至4.77 mmol/l，而对照组无变化。运动使两组的AMPK α 2活性在20分钟时显著增加2.7倍，并且在整个方案中保持升高，但运动对AMPK α 1活性没有影响。与对照组相比，2型糖尿病患者肌肉中AMPK α 1、α 2和β 1的蛋白表达相似。AMPK α 2在两组的肌肉中约占总α mRNA的三分之二。总之，2型糖尿病患者运动诱导的AMPK α 2活性正常，α 1、α 2和β 1亚型表达正常。AMPK的药理学激活可能是治疗2型糖尿病的一个有吸引力的靶点。
Insulin-stimulated GLUT4 translocation is impaired in people with type 2 diabetes. In contrast, exercise results in a normal increase in GLUT4 translocation and glucose uptake in these patients. Several groups have recently hypothesized that exercise increases glucose uptake via an insulin-independent mechanism mediated by the activation of AMP-activated protein kinase (AMPK). If this hypothesis is correct, people with type 2 diabetes should have normal AMPK activation in response to exercise. Seven subjects with type 2 diabetes and eight matched control subjects exercised on a cycle ergometer for 45 min at 10% of maximum workload. Biopsies of vastus lateralis muscle were taken before exercise, after 20 and 45 min of exercise, and at 30 min postexercise. Blood glucose concentrations decreased from 7.6 to 4.77 mmol/l with 45 min of exercise in the diabetic group and did not change in the control group. Exercise significantly increased AMPK alpha2 activity 2.7-fold over basal at 20 min in both groups and remained elevated throughout the protocol, but there was no effect of exercise on AMPK alpha1 activity. Subjects with type 2 diabetes had similar protein expression of AMPK alpha1, alpha2, and beta1 in muscle compared with control subjects. AMPK alpha2 was shown to represent approximately two-thirds of the total alpha mRNA in the muscle from both groups. In conclusion, people with type 2 diabetes have normal exercise-induced AMPK alpha2 activity and normal expression of the alpha1, alpha2 and beta1 isoforms. Pharmacological activation of AMPK may be an attractive target for the treatment of type 2 diabetes.