Endurance, or “aerobic” exercise, is generally viewed as cardiovascular exercise and is not generally associated with skeletal muscle hypertrophy. Endurance exercise is defined as exerting a low-intensity load on a muscle over a long period of time, such as the effect of jogging on the calf muscles but also encompasses the use of light weights in resistance exercise. However, a recent study, which elucidates the skeletal muscle pathologies in diabetic rats, discovered the hypertrophic effect of endurance exercise (in this case, treadmill running on the gastrocnemius muscle), even on non-diabetic rats. It also details two specific skeletal muscle proteins, Kinesin Family Member 5B (KIF5B) and Growth Associated Protein 43 (GAP-43), their dysfunction in diabetes and how endurance exercise promotes skeletal muscle hypertrophy through these specific protein pathways.
In this study, 52 male rats were divided into 4 groups: controls (healthy, non-diabetic), endurance-trained controls, diabetics, endurance-trained diabetics. K1F5B, GAP-43 and PAX7 (muscle satellite cells which are responsible for muscle regeneration after exercise-induced muscle damage2) abundance, as well as gastrocnemius cross-sectional area (CSA) were calculated.
The diabetic untrained group had significantly lower gastrocnemius CSA compared the control untrained group, and almost half the number of muscle nuclei (myonuclei) and almost a third of the satellite cell (PAX7) abundance of the control untrained group. This signifies major pathologies in skeletal muscle of diabetics. However, the diabetic trained group had significantly better parameters of muscle health, and had almost the same CSA, myonuclei and PAX7 abundance as untrained controls, suggesting the significant hypertrophic effect of endurance-training a muscle and the potential in therapeutically countering the diabetes-induced muscle pathologies. The trained healthy controls had significantly superior muscle parameters to all other groups, with notably higher CSA, and myonuclei and PAX7 abundance.
The KIF5B protein was significantly positively correlated with myonuclei number and muscle CSA. KIF5B was moderately supressed in diabetes and endurance-training significantly increased the protein. KIF5B is believed to be responsible for positioning of myonuclei in the muscle (muscles have multiple nuclei unlike most other cell types and new myonuclei can be created even in adults via methods such as resistance exercise3). Furthermore, the GAP-43 protein was also significantly positively correlated with myonuclei number and muscle CSA. GAP-43 was also moderately suppressed in diabetes and endurance-training significantly increased the protein. GAP-43 is believed to be involved in calcium-handling regulation. Therefore, the upregulation of both proteins locally in the gastrocnemius muscle via endurance-training of the muscle seems to provide hypertrophic effect, potentially through these protein pathways and this research also shed light on potential causes of skeletal muscle dysfunctions such as atrophy observed in diabetes patients.
- Rahmati, M., Taherabadi, S.J. 2021. The effects of exercise training on Kinesin and GAP-43 expression in skeletal muscle fibers of STZ-induced diabetic rats. Sci Rep 11, 9535. https://doi.org/10.1038/s41598-021-89106-6
- Sambasivan R, Yao R, et al 2011. Pax7-expressing satellite cells are indispensable for adult skeletal muscle regeneration. Development. 2011 Sep;138(17):3647-56. doi: https://doi.org/10.1242/dev.067587 . Erratum in: Development. 2011 Oct;138(19):4333. PMID: 21828093.
- Bruusgaard J.C, Johansen I.B., et al 2010. Myonuclei acquired by overload exercise precede hypertrophy and are not lost on detraining. Proceedings of the National Academy of Sciences Aug 2010, 107 (34) 15111-15116; DOI: https://doi.org/10.1073/pnas.0913935107