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/mm2), 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.

Comment on Prior et al. Increased Skeletal Muscle Capillarization Independently Enhances Insulin Sensitivity in Older Adults After Exercise Training and Detraining. Diabetes 2015;64:3386–3395

“…In this respect, the authors could have additionally accounted for HDL cholesterol, which has been associated with insulin-mediated microvascular vasomotion facilitating nutrient and hormone delivery (2) and insulin sensitivity (3). Interestingly, HDL cholesterol levels were increased with training and remained elevated after detraining, matching the pattern observed for insulin sensitivity (1).…”

“…I read with great interest the recent article by Prior et al (1), in which muscle biopsies and the hyperinsulinemiceuglycemic clamp were combined to interrogate the role of the exercise-induced increase in skeletal muscle capillarization on insulin sensitivity. Specifically, the effects of 6 months of endurance training and 2 weeks of detraining on intramuscular signaling, capillarization, and whole-body insulin sensitivity were determined in older sedentary individuals.…”

“…The second issue concerns the exclusive use of CD (capillaries per mm 2 of muscle area) as the measure of skeletal muscle capillarization (1). In this regard, although muscle fiber areas were unaltered with training and detraining (1), changes in CD may be also influenced by those of the muscle interstitial area (4), which were not documented (1).…”

“…This study represents a further step toward understanding the mechanisms underlying the beneficial effects of exercise training on insulin sensitivity and glucose tolerance. Here, I would like to address two issues that may buttress, or perhaps moderate, the main conclusion of the accomplished work of Prior et al (1).…”

Response to Comment on Prior et al. Increased Skeletal Muscle Capillarization Independently Enhances Insulin Sensitivity in Older Adults After Exercise Training and Detraining. Diabetes 2015;64:3386–3395

“…We thank Dr. Montero for his insightful comment (1) on our recent article (2). His comment raises two interesting questions regarding the finding that increases in skeletal muscle capillary density (CD) contribute to exercise training-induced increases in insulin sensitivity (M/I).…”