Skeletal muscle loss exacerbated by diabetes improved with oligo DNA

Use of myoDN to improve muscle differentiation deteriorated by diabetes mellitus. Photo credit: Tomohide Takaya, Shinshu University

The skeletal muscle is the largest organ in the body. It makes up 30 to 40% of body weight and is 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, one group looked at whether myoDN improved myoblast differentiation, which is made worse 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.

myoDN restores impaired muscle differentiation in patients with type 1 and type 2 diabetes. Photo credit: Modified from Nakamura et al., Frontiers in Physiology (2021) 12: 679152

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.

Identification of oligo DNA that promotes skeletal muscle differentiation

More information:
Shunichi Nakamura et al., Myogenic Oligodeoxynucleotide (myoDN), Restores Differentiation of Skeletal Muscle Myoblasts Worsened by Diabetes Mellitus, Frontiers in Physiology (2021). DOI: 10.3389 / fphys.2021.679152

Provided by Shinshu University

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