AMP-activated protein kinase (AMPK) is activated in muscle of subjects with type 2 diabetes during exercise

Insulin-stimulated GLUT4 translocation is impaired in people with type 2 di abetes. In contrast, exercise results in a normal increase in GLUT4 translo cation and glucose uptake in these patients. Several groups have recently h ypothesized that exercise increases glucose uptake via an insulin-independe nt mechanism mediated by the activation of AMP-activated protein kinase (AM PK). 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-fo ld 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. Sub jects with type 2 diabetes had similar protein expression of AMPK alpha1, a lpha2, 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 no rmal exercise-induced AMPK alpha2 activity and normal expression of the alp ha1, alpha2 and beta1 isoforms. Pharmacological activation of AMPK may be a n attractive target for the treatment of type 2 diabetes.