Small but mighty: The importance of the microvasculature for exercise and metabolism

4 February 2021

By Lewan Parker (@lewan_parker) and Michelle Keske (@KeskeMichelle), Institute for Physical Activity and Nutrition (IPAN), Deakin University, Australia

The smallest blood vessels in our body, often called the microvasculature, are just as important as larger arteries or the heart when it comes to maintaining health and preventing conditions such as cardiovascular disease and type 2 diabetes.

These tiny blood vessels (many are invisible to the naked eye) do not cope well with high blood-sugar levels, regardless of where they are in the body, so this is also true for the ones located within our skeletal muscle.

In a vicious cycle, poor microvascular health in skeletal muscle is linked to impaired removal of sugar from the blood stream which further contributes to the development of chronic disease and microvascular complications.

Previous research from our team indicated that many of the health complications of Type 2 diabetes, including impaired ability to exercise and elevated blood sugar levels may, at least in part be a result of impairments in the microvasculature rather than impairments in large artery or heart health (1, 2).

Recently, our paper published in The Journal of Physiology showed that even in healthy adults, consuming a high-sugar meal or drink leads to a substantial decrease in microvascular blood flow in skeletal muscle which persists for at least 2 hours (3).

Although we had established that exercise and skeletal muscle contraction are potent stimuli for increasing muscle microvascular blood flow (4, 5), this is the first study to investigate whether exercise could enhance muscle microvascular blood flow during and after eating a high-sugar meal.

This study was conducted at the Institute for Physical Activity and Nutrition (IPAN), Deakin University’s clinical research facility.

To investigate how exercise influences blood flow following a high-sugar meal, we designed a study where participants consumed the meal in the morning on a rest day (no exercise beforehand), and on a separate occasion consumed the exact same meal 3 and 24 hours after cycling for 1 hour on an exercise bike.

We used an ultrasound machine to visualise and measure blood flow in both the large artery and microvasculature of the thigh. We used an advanced technique called contrast-enhanced ultrasound that allowed us to directly measure microvascular blood flow in human skeletal muscle.

This technique involves the infusion of a liquid (called a contrast agent) via a vein in the arm. This liquid then circulates throughout the body, including the microvasculature in muscle, and allows us to see the microvasculature using a commercial ultrasound machine. This is advantageous as it allows us to directly see and measure blood flow dynamics within the smaller blood vessels of the muscle in real-time.

Our new study shows for the first time that undertaking moderate-intensity exercise almost doubles muscle microvascular blood flow when a high-sugar meal is consumed 3 hours after exercise. Furthermore, we revealed that the decrease in microvascular blood flow elicited by the high-sugar meal was reduced when the meal was ingested after exercise. These findings are important as they suggest that a single session of exercise can have lasting beneficial effects on microvascular blood flow in skeletal muscle.

Exercise may therefore be an effective strategy for improving microvascular blood flow during situations that elevate blood sugar levels or impair vascular function, such as Type 2 diabetes, or high-sugar consumption in both healthy and clinical populations.

Another interesting observation was that microvascular blood flow responses in the muscle of the leg did not necessarily reflect changes that occurred in the large artery of the leg. In some cases, these blood flow responses went in the opposite direction. Although it is not yet clear how, these findings support our previous reports that large artery and microvascular blood flow can operate independent of each other.

These findings contribute to the growing evidence that all levels of the vascular network in humans (from the heart to the microvasculature) needs to be studied to provide a more accurate and comprehensive understanding of vascular function in humans and the relationship to health and disease.

One limitation of our research is that we were unable to directly link the increase in muscle microvascular blood flow after exercise to that of enhanced metabolism of the meal. To truly understand how a meal is metabolised after exercise, additional advanced procedures and techniques are required.

Another important limitation is that we only recruited males for this study. Males and females may exhibit different vascular responses to exercise and food consumption, and as such we need to confirm these findings in females. This is something we are now exploring.

Findings from this study have led to several other research questions that we are now investigating. Our primary focus is to explore and investigate how a single session of exercise, and long-term exercise training, can be optimised and used to improve skeletal muscle microvascular health, and subsequently improve exercise tolerance and meal metabolism in patients with Type 2 diabetes.

This project is a collaborative effort between the Institute for Physical Activity and Nutrition (IPAN) at Deakin University and the Baker Heart and Diabetes Institute, and is funded by the NHMRC and National Heart Foundation of Australia.

We are also currently investigating specific mechanisms that may explain how and why high blood-sugar levels lead to poor microvascular health in skeletal muscle. Confirming that the increase in microvascular blood flow after exercise is directly related to improved meal metabolism is also a priorityå of our research team.

Please note that all views expressed on The Physiological Society’s blog reflect those of the author(s) and not of The Society.

References

  1. Sacre, J. W., Jellis, C. L., Haluska, B. A., Jenkins, C., Coombes, J. S., Marwick, T. H., & Keske, M. A. (2015). Association of Exercise Intolerance in Type 2 Diabetes With Skeletal Muscle Blood Flow Reserve. JACC. Cardiovascular Imaging, 8(8), 913-921. doi: 10.1016/j.jcmg.2014.12.033 
  2. Russell, R. D., Hu, D., Greenaway, T., Blackwood, S. J., Dwyer, R. M., Sharman, J. E., Jones, G., Squibb, K. A., Brown, A. A., Otahal, P., Boman, M., Al-Aubaidy, H., Premilovac, D., Roberts, C. K., Hitchins, S., Richards, S. M., Rattigan, S., & Keske, M. A. (2017). Skeletal Muscle Microvascular-Linked Improvements in Glycemic Control From Resistance Training in Individuals With Type 2 Diabetes. Diabetes Care, 40(9), 1256-1263. doi: 10.2337/dc16-2750 
  3. Parker, L., Morrison, D. J., Wadley, G. D., Shaw, C. S., Betik, A. C., Roberts-Thomson, K., Kaur, G., & Keske, M. A. (2021). Prior exercise enhances skeletal muscle microvascular blood flow and mitigates microvascular flow impairments induced by a high-glucose mixed meal in healthy young men. J Physiol, 599(1), 83-102. doi: 10.1113/JP280651 
  4. Betik, A. C., Parker, L., Kaur, G., Wadley, G. D., & Keske, M. A. (2021). Whole-Body Vibration Stimulates Microvascular Blood Flow in Skeletal Muscle. Med Sci Sports Exerc, 53(2), 375-383. doi: 10.1249/MSS.0000000000002463 
  5. Vincent, M. A., Clerk, L. H., Lindner, J. R., Price, W. J., Jahn, L. A., Leong-Poi, H., & Barrett, E. J. (2006). Mixed meal and light exercise each recruit muscle capillaries in healthy humans. Am J Physiol Endocrinol Metab, 290(6), E1191-1197. doi: 10.1152/ajpendo.00497.2005 

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