High-Intensity Interval Training Restores Glycolipid Metabolism and Mitochondrial Function in Skeletal Muscle of Mice With Type 2 Diabetes

Abstract

High-intensity interval training has been reported to lower fasting blood glucose and improve insulin resistance of type 2 diabetes without clear underlying mechanisms. The purpose of this study was to investigate the effect of high-intensity interval training on the glycolipid metabolism and mitochondrial dynamics in skeletal muscle of high-fat diet (HFD) and one-time 100 mg/kg streptozocin intraperitoneal injection-induced type 2 diabetes mellitus (T2DM) mice. Our results confirmed that high-intensity interval training reduced the body weight, fat mass, fasting blood glucose, and serum insulin of the T2DM mice. High-intensity interval training also improved glucose tolerance and insulin tolerance of the T2DM mice. Moreover, we found that high-intensity interval training also decreased lipid accumulation and increased glycogen synthesis in skeletal muscle of the T2DM mice. Ultrastructural analysis of the mitochondria showed that mitochondrial morphology and quantity were improved after 8 weeks of high-intensity interval training. Western blot analysis showed that the expression of mitochondrial biosynthesis related proteins and mitochondrial dynamics related proteins in high-intensity interval trained mice in skeletal muscle were enhanced. Taken together, these data suggest high-intensity interval training improved fasting blood glucose and glucose homeostasis possibly by ameliorating glycolipid metabolism and mitochondrial dynamics in skeletal muscle of the T2DM mice.

Effects of two workload-matched high intensity interval training protocols on regulatory factors associated with mitochondrial biogenesis in the soleus muscle of diabetic rats

“…Our results indicate that both DHIIT training protocols reduced FBS levels to a similar extent, suggesting that either a 1 or 2 min of recovery time improved fasting blood glucose levels and reduced FBS levels in both groups to the same extent. These observations are consistent with previous findings that HIIT reduces hyperglycemia in diabetic patients (Little et al, 2011a;Alvarez et al, 2016) and rodents (Chavanelle et al, 2017;Zheng et al, 2020). Insulin-stimulated GLUT-4 translocation is disrupted in diabetes, and exercise training stimulates the translocation of GLUT-4 to the muscle cell membrane in diabetic patients (Kennedy et al, 1999;O'Gorman et al, 2006).…”

“…We provide novel findings on the effects of two different HIIT protocols on the regulation of PGC-1α protein and gene expression in diabetic rats. The observed increases in the expression levels of PGC-1α protein produced by HIIT were supported by other studies in obese rats (Khalafi et al, 2020), diabetic mice (Zheng et al, 2020), and humans (Hood et al, 2011). Although the molecular mechanisms by which HIIT induces mitochondrial signaling pathways are unclear, there is some evidence that the intermittent effort and the reoccurrence of metabolic fluctuations in the skeletal muscle may play a role (Combes et al, 2015).…”

“…However, we did not find a greater elevation in PGC-1α protein, and the higher increase in PGC-1α gene expression in the DHIIT2:1 group did not result in a higher increase in protein expression. The difference in protein expression would likely have been noticed if there had been additional weeks of training, especially given that other studies found an increase in PGC-1α protein in the muscle tissue of the animals following 8 weeks of HIIT (Zheng et al, 2020;Heiat et al, 2021). In response to frequent muscular contractions, fluctuations in the cytosolic concentration of numerous metabolites (including increased ADP:ATP ratios, Ca 2+ flux, ROS generation, and redox status) regulate the expression of genes encoding proteins involved in mitochondrial biogenesis (MacInnis and Gibala, 2017).…”

A Meta-Analysis of High-Intensity Interval Training on Glycolipid Metabolism in Children With Metabolic Disorders

“…It was followed in animal experiments that the improvement of BG and BI in T2D mice after 8-week HIIT accompanied by the increase of glycogen content in skeletal muscle ( 48 ). Some studies have shown that upregulation of GLUT4, increased aerobic enzyme activity, and mitochondrial biogenesis may be a potential mechanism of HIIT promoting glucose uptake and improving insulin sensitivity ( 17 , 50 – 52 ).…”

Metabolic Flexibility and Its Impact on Health Outcomes

“…The potent effect of exercise to increase GLUT4 expression not only enhances insulin action but facilitates muscle glycogen storage following exercise training. 65 The increase in energy demand brought about by exercise is also a potent stimulus to increase mitochondrial function and content. 66 Studies in both humans and rodents have found strong associations between the level of physical activity and changes in mitochondrial content and function.…”