Increased Skeletal Muscle Capillarization Independently Enhances Insulin Sensitivity in Older Adults After Exercise Training and Detraining

Abstract

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.

Figures

Figure 1

Study design. CT, computed tomography.

Figure 2

Changes in insulin sensitivity (M/I) after exercise training and detraining. M/I was measured after a 12-h overnight fast using a 3-h hyperinsulinemic-euglycemic glucose clamp (n = 12). Data are reported as means ± SEM during the third hour of the clamp (micromoles of glucose infused per kilogram of fat-free mass per picomole of plasma insulin per minute). *Significant difference from baseline, P < 0.05. mo, month.

Figure 3

Changes in skeletal muscle GLUT4 and AMPKα1 (A), Akt (B), and pAktSer473 (C) expression, as well as the pAktSer473-to-Akt ratio (D), after exercise training and detraining. Levels of GLUT4, AMPKα1, total Akt, and pAktSer473 proteins were determined in vastus lateralis by Western blot analyses. Representative Western blots are shown directly above the corresponding bars in each graph. Protein expression levels were determined by densitometry of the chemiluminescence signal and are expressed as arbitrary units (AU). Data are presented as means ± SEM (n = 12). *Significant difference from baseline, P < 0.05. †Significant difference from basal condition (without insulin stimulation) at the same time point, P < 0.01. mo, month.

Figure 4

Changes in skeletal muscle CD after exercise training and detraining. CD was measured in vastus lateralis samples by immunohistochemistry and expressed as capillaries per square millimeter of muscle cross-sectional area. Data are reported as means ± SEM (n = 12). *Significant difference from baseline, P < 0.05. mo, month.

Figure 5

Scatterplot depicting the partial correlation between the differences in insulin sensitivity (M/I) and skeletal muscle CD between the baseline and detraining time points. Data are transformed residuals from the regression analysis accounting for sex and percentage of body fat (model R = 0.82; P = 0.02; n = 12). AU, arbitrary unit.

Figure 6

Summary of the measured contributors to increases in insulin sensitivity (M/I) after aerobic exercise training and detraining. mo, month; p-Akt, phosphorylated AktSer473.