Skeletal muscle is the primary tissue for glucose disposal, which is regulated primarily by insulin. When insulin binds to its receptors on muscle cells, it stimulates the movement of GLUT4 from within the cell to the cell membrane so that glucose may enter and be dealt with accordingly. Interestingly enough, in healthy individuals, insulin also acts upon the endothelial cells of blood vessels as a vasodilator, and insulin-stimulated blood flow has been shown to account for up to 40% of glucose uptake.

On this note, previous research has shown that short-term reductions in physical activity in otherwise healthy people lead to increased post-prandial blood glucose levels, as well as impaired endothelial function. Yet it is unclear if these outcomes occur simultaneously or whether one precedes the other. Thus, Reynolds et al. from the University Of Missouri School Of Medicine recently conducted an intervention of healthy, recreationally active, young men to better understand how sedentariness may impact insulin sensitivity and glucose tolerance.

All the subjects were habitually active, defined as performing at least 90 minutes/day or aerobic exercise on more than three days/week as well as taking >10,000 pedometer verified steps (which shouldn’t be difficult by any means if they are running, or even walking, for 90 minutes). The entire study lasted ten days as outlined in the image below, and all food was provided by the laboratory to help standardize potential insulin-influencing variables. As can be seen in the image, after a 3 day pre-intervention phase, the subjects were instructed to refrain from all structured exercise, take the elevator instead of stairs, and park closer to doors so as to limit step counts to about 5,000 per day for the next five days. The study ended with a one-day return to pre-intervention activity levels and more testing to see how this sudden increase in activity influenced glucose tolerance.

All in all the step count dropped from around 12k per day to 4k, but insulin-stimulated blood flow was completely unaffected. Where the change occurred was in the insulin response that was shown to be significantly greater after the 5-day reduction of physical activity when compared to baseline. Insulin sensitivity as measured by the Matsuda index was also significantly lower and neither of these outcomes returned to baseline values after a single exercise session and return to normal physical activity following the reduced physical activity period. This was all confirmed by the continuous glucose monitoring device that showed impairments in free-living glycemic control with physical inactivity (see image: BL, baseline; RA5, reduced activity; RTA1, return to activity).

Reminders are important, and in this case the reminder is to go for a walk… or three

This study by Reynolds et al. provides us with two main takeaways:

1. Impairments of glucose tolerance in response to reduced physical activity are not paralleled by reductions in insulin-stimulated blood flow, and
2. A one-day return to higher (and habitual) physical activity levels after five days of reduced activity is not sufficient to restore normal glycemic control or insulin sensitivity.

The first takeaway is in direct contrast to the previously mentioned study showing insulin-stimulated blood-flow to account for upwards of 40% of glucose uptake in healthy individuals. This suggests that physical inactivity may work its magic through factors other than blood flow. It is tempting to suggest that perhaps the reduction of insulin sensitivity was mediated through reductions in GLUT4 transporter concentrations, which has been demonstrated in endurance athletes after six days of detraining. However, there is strong evidence showing that a single bout of exercise increases GLUT4 expression independent of insulin in both healthy and diseased muscles, and the one-day return to habitual activity that included a 45-minute exercise bout did not restore insulin sensitivity or glycemic control.

Rather, Reynolds et al. suggests that it is possibly changes within the skeletal muscle microcirculation rather than arterial blood flow that led to impaired glucose tolerance. This is certainly supported by research showing that modest hyperglycemia can impair the dispersion of insulin through the interstitial space of muscle cells and consequently reduce the ability of insulin to bind to and signal its receptors.

Regardless of the mechanism, the bottom line is simple. Being less physically active impairs glucose tolerance.

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