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 70% 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 ␣2 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 ␣1 activity. Subjects with type 2 diabetes had similar protein expression of AMPK ␣1, ␣2, and ␤1 in muscle compared with control subjects. AMPK ␣2 was shown to represent approximately two-thirds of the total ␣ mRNA in the muscle from both groups. In conclusion, people with type 2 diabetes have normal exercise-induced AMPK ␣2 activity and normal expression of the ␣1, ␣2 and ␤1 isoforms. Pharmacological activation of AMPK may be an attractive target for the treatment of type 2 diabetes. Diabetes 50:921-927, 2001

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