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- Musi, N., et al.
(författare)
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AMP-activated protein kinase (AMPK) is activated in muscle of subjects with type 2 diabetes during exercise
- 2001
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Ingår i: Diabetes. - Alexandria, VA, USA : American Diabetes Association Inc.. - 0012-1797 .- 1939-327X. ; 50:5, s. 921-927
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Tidskriftsartikel (refereegranskat)abstract
- 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 α2 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 α1 activity. Subjects with type 2 diabetes had similar protein expression of AMPK α1, α2, and β1 in muscle compared with control subjects. AMPK α2 was shown to represent approximately two-thirds of the total a mRNA in the muscle from both groups. In conclusion, people with type 2 diabetes have normal exercise-induced AMPK α2 activity and normal expression of the α1, α2 and β1 isoforms. Pharmacological activation of AMPK may be an attractive target for the treatment of type 2 diabetes.
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| 2. |
- Musi, N., et al.
(författare)
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Metformin increases AMP-activated-protein-kinase activity in skeletal of subjects with type 2 diabetes
- 2002
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Ingår i: Diabetes. - Alexandra, VA, USA : American Diabetes Association Inc.. - 0012-1797 .- 1939-327X. ; 51:7, s. 2074-2081
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Tidskriftsartikel (refereegranskat)abstract
- Metformin is an effective hypoglycemic drug that lowers blood glucose concentrations by decreasing hepatic glucose production and increasing glucose disposal in skeletal muscle; however, the molecular site of metformin action is not well understood. AMP-activated protein kinase (AMPK) activity increases in response to depletion of cellular energy stores, and this enzyme has been implicated in the stimulation of glucose uptake into skeletal muscle and the inhibition of liver gluconeogenesis. We recently reported that AMPK is activated by metformin in cultured rat hepatocytes, mediating the inhibitory effects of the drug on hepatic glucose production. In the present study, we evaluated whether therapeutic doses of metformin increase AMPK activity in vivo in subjects with type 2 diabetes. Metformin treatment for 10 weeks significantly increased AMPK α2 activity in the skeletal muscle, and this was associated with increased phosphorylation of AMPK on Thr172 and decreased acetyl-CoA carboxylase-2 activity. The increase in AMPK α2 activity was likely due to a change in muscle energy status because ATP and phosphocreatine concentrations were lower after metformin treatment. Metformin-induced increases in AMPK activity were associated with higher rates of glucose disposal and muscle glycogen concentrations. These findings suggest that the metabolic effects of metformin in subjects with type 2 diabetes may be mediated by the activation of AMPK α2.
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