The skeletal muscle is the largest organ in the body, making up 30 to 40% of the body’s weight and responsible for various functions such as energy metabolism and heat generation.
However, in some diabetics, skeletal muscle mass is reduced and this muscle loss is correlated with mortality. It has been reported that the differentiation of myoblasts, which are the muscle progenitor cells, is decreased in diabetics and this is believed to be one of the underlying causes of muscle loss.
Shinshu University’s assistant professor Tomohide Takaya recently reported that oligo-DNA, derived from the genomic sequence of lactic acid bacteria, promotes differentiation in skeletal muscle by binding to the target protein nucleolin in myoblasts.
This “muscle-building oligo-DNA” (myoDN) can be used in nucleic acid drugs for various muscle diseases. In this study, the group investigated whether myoDN improved myoblast differentiation aggravated by diabetes.
Myoblasts collected from healthy volunteers, patients with type 1 diabetes, and patients with type 2 diabetes were used for this experiment. Compared to healthy volunteers, diabetic myoblasts had a reduced ability to differentiate into skeletal muscles.
Remarkably, the administration of myoDN improved the differentiation of skeletal muscles exacerbated by diabetes. The group also found that glucose and fatty acids, which are elevated in the blood of diabetics, trigger an inflammatory response in myoblasts, and myoDN suppresses these inflammatory responses.
It is believed that myoDN is a nucleic acid molecule that is effective in reducing muscle mass associated with diabetics. There is currently no effective therapeutic agent for muscle wasting and the action of myoDN, which promotes skeletal muscle differentiation, is unique. myoDN is effective in healthy subjects with different backgrounds and in type 1 and type 2 patients. On the other hand, the analysis using multiple myoblasts revealed that there are individual differences in the effects of myoDN, and questions for clinical application were also clarified.
In the future, the scope and test must be expanded in order to clarify the cause of individual differences. Diseases other than diabetes like cancer and heart failure also cause muscle wasting. The group hopes to investigate whether myoDN also promotes the differentiation of the skeletal muscles in these diseases. The ultimate goal is to use myoDN as an effective nucleic acid drug against muscle wasting associated with various diseases.
Nakamura, S. et al. (2021) Myogenic oligodeoxynucleotide (myoDN) restores the differentiation of myoblasts of the skeletal muscles that have been impaired by diabetes mellitus. Limits in Physiology. doi.org/10.3389/fphys.2021.679152.