Are Myokines Linked to Metabolic Improvements with Increased Physical Activity in Subjects with Type 2 Diabetes: How Acute and Chronic Exercise Regulate Myokine Secretion in this Population

Abstract

Skeletal muscle is the main site of post-prandial glucose uptake and in patients with type 2 diabetes (T2D), it is affected with metabolic dysfunctions. Muscle cells secrete peptides called myokines that positively modulate muscle metabolism. In patients with T2D, myokine secretion is altered. As physical activity is an efficient method for the management of T2D that can also regulate myokine secretion, regular practice of exercise could be beneficial to patients with T2D in restoring myokine secretion. To study this potential relationship, we explored the regulation of myokines in humans with or without T2D in response to acute and chronic exercise. We first compared peripheral myokines in subjects with or without obesity in response to an exercise bout, and found that plasma FGF21, interleukin (IL)-6, IL-8, IL-15, and IL-18 were regulated by acute exercise, while obesity was associated with elevated plasma IL-13, but lower IL-8 and FGF21. Chronic inflammation is a common driver of both coronary artery disease (CAD) and T2D. The comparison of peripheral cytokines (candidate myokines) in subjects with CAD with or without T2D in response to interventions consisting of either high intensity interval training (HIIT) or moderate intensity continuous training (MICT) showed that the co-morbidity was associated with increased plasma IL-8 and training further reduced plasma FGF21 and IL-6 in this group. No differences were found between HIIT and MICT on cytokine secretion. Finally, we compared the effect of chronic exercise on peripheral and local myokine secretion in healthy subjects and patients with T2D with or without resistance to exercise training and found no differences as a function of T2D status or response to exercise, with the exception of modest differences in expression patterns for certain myokines (IL-1β, IL-8, IL-10, and IL-15). This research serves as comparative reference of how autocrine/paracrine and endocrine signaling by skeletal muscle is altered by exercise in patients with T2D. Most studies concerning myokines and their role in modulating energy metabolism mostly focus on a single candidate at a time, the results of my doctoral research are novel in considering the myokine network without neglecting the potential interactions in action of these peptides.