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- Title
Glucose Metabolism and Skeletal Muscle Akt and AS160 Phosphorylation after Weight Loss and Endurance Training.
- Authors
Joseph, Lyndon J.; Prior, Steven J.; McLenithan, John C.; Ryan, Alice S.
- Abstract
Phosphorylation of Akt Substrate 160 (AS 160) by Akt and other kinases is the most proximal step in the regulation of GLUT4 translocation and glucose uptake. Akt and AS 160 phosphorylation increases after acute aerobic exercise and is associated with increased glucose transport in rodent models. We hypothesized that chronic weight loss and aerobic training (WL+AEX) would increase human skeletal muscle Akt and AS 160 phosphorylation with associated improvements in glucose utilization. To test this hypothesis, we measured in vivo glucose utilization (M: 3-hr 80 mU/m²/min euglycemic-hyperinsulinemic clamp) and basal and insulin-stimulated phosphorylation of Akt and AS 160 in vastus lateralis muscle biopsies (taken 120 min into the clamp) before and after 6-month WL+AEX (clamp and biopsies 36-48 hrs after exercise) in 10 non-diabetic men (age = 66 ± 6 yrs). Men were overweight/obese (BMI = 30 ± 4 kg/m²; % fat = 32 ±10 %; X ± SD) and sedentary (VO[sub 2]max = 20 ± 4 ml/kg/min). Aerobic capacity increased by 23% (p < 0.01), and body weight and fat mass (DXA) decreased by 7% and 21%, respectively (p < 0.05) after WL+AEX. M increased by 29% (39 ± 13 vs. 51 ± 15 umol/kg[sub BW]/min) and M/I increased by 38% (0.037 ± .016 to 0.051 ± 0.019 umol/kg[sub BW]/min/pmol; an index of insulin sensitivity). Both fasting glucose (98 ± 8 vs. 91 ± 6 mg/dl; p < 0.01), and insulin (93 ± 38 vs. 67 ± 22 pmol/ml; p < 0.05) decreased with WL+AEX. Hyperinsulinemia increased phosphorylation of Akt (6-fold; p < 0.01 and 7-fold; p < 0.01)) and AS160 (l.9-fold; p < 0.05 and 1.5-fold; p = 0.09) before and after the intervention respectively. The insulin stimulated increase in Akt and AS 160 phosphorylation did not change with WL+AEX. Neither the change in M nor M/I after WL+AEX was associated with the changes in Akt and AS 160 phosphorylation. In contrast to acute exercise in rodents, our results suggest that the improvement in glucose utilization after chronic WL+AEX in older men may not be mediated by increased activation of Akt and AS160 measured 36-48 hours after exercise training.
- Subjects
BLOOD sugar; MUSCULOSKELETAL system; PROTEIN kinases; PHOSPHORYLATION; WEIGHT loss; AEROBIC exercises; PHYSICAL training &; conditioning
- Publication
Diabetes, 2007, Vol 56, pA281
- ISSN
0012-1797
- Publication type
Article