Intramuscular signaling and glucose transport mechanisms contribute to improvements in insulin sensitivity after aerobic exercise training. This study tested the hypothesis that increases in skeletal muscle capillary density (CD) also contribute to exercise-induced improvements in whole-body insulin sensitivity (insulin-stimulated glucose uptake per unit plasma insulin [M/I]) independent of other mechanisms. The study design included a 6-month aerobic exercise training period followed by a 2-week detraining period to eliminate short-term effects of exercise on intramuscular signaling and glucose transport. Before and after exercise training and detraining, 12 previously sedentary older (65 ± 3 years) men and women underwent research tests, including hyperinsulinemic-euglycemic clamps and vastus lateralis biopsies. Exercise training increased Vo2max (2.2 ± 0.2 vs. 2.5 ± 0.2 L/min), CD (313 ± 13 vs. 349 ± 18 capillaries/mm(2)), and M/I (0.041 ± 0.005 vs. 0.051 ± 0.007 μmol/kg fat-free mass/min) (P < 0.05 for all). Exercise training also increased the insulin activation of glycogen synthase by 60%, GLUT4 expression by 16%, and 5' AMPK-α1 expression by 21%, but these reverted to baseline levels after detraining. Conversely, CD and M/I remained 15% and 18% higher after detraining, respectively (P < 0.05), and the changes in M/I (detraining minus baseline) correlated directly with changes in CD in regression analysis (partial r = 0.70; P = 0.02). These results suggest that an increase in CD is one mechanism contributing to sustained improvements in glucose metabolism after aerobic exercise training.
Trial registration: ClinicalTrials.gov NCT00701051.
© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.