Study examines if myoDN improves myoblast differentiation exacerbated by diabetes

Skeletal muscle, the largest organ in the human body, makes up 30% to 40% of body weight and serves multiple functions like heat production and energy metabolism.

myoDN recovers the impaired muscle differentiation of patients with type 1 and type 2 diabetes. Image Credit: Modified from Nakamura et al., Frontiers in Physiology (2021).

But in some diabetics, skeletal muscle mass tends to reduce and that muscle loss is correlated with mortality. Researchers report that the differentiation of myoblasts—the muscle precursor cells—is decreased in diabetic patients, and this is considered to be one of the fundamental causes of muscle loss.

Tomohide Takaya, Assistant Professor from Shinshu University, recently noted that oligo DNA extracted from the genome sequence of lactic acid bacteria promotes differentiation into skeletal muscle by attaching to the target protein nucleolin in myoblasts.

This “muscle-forming oligo DNA” (myoDN) could hold the potential for use in nucleic acid drugs for different muscle diseases. As part of this study, the team investigated whether myoDN enhances the differentiation of myoblasts, which is exacerbated by diabetes.

Myoblasts gathered from healthy subjects, patients with type 1 diabetes, and patients with type 2 diabetes were used for this experiment. When compared to healthy subjects, diabetic myoblasts had a decreased ability to differentiate into skeletal muscle.

Most significantly, the administration of myoDN enhanced skeletal muscle differentiation exacerbated by diabetes. The team also discovered that fatty acids and glucose, which are increased in the blood of diabetic patients, lead to an inflammatory response in myoblasts, and myoDN inhibits these inflammatory responses.

Researchers consider that myoDN is a nucleic acid molecule effective in decreasing muscle mass related to diabetics. At present, there is no effective therapeutic agent for muscle wastage, and the function of myoDN, which promotes the differentiation of skeletal muscles, is exclusive.

myoDN proves effective for healthy subjects with different backgrounds as well as type 1 and type 2 patients. By contrast, analysis with several myoblasts showed that there are individual differences in the effects of myoDN, and challenges in the clinical application were also clarified.

Going forward, it will be essential to widen the scope and test to clarify the cause of individual differences. Diseases apart from diabetes, like heart failure and cancer, also lead to muscle wastage. The team believes that it can verify whether myoDN promotes the differentiation of skeletal muscles in these diseases as well. The eventual sim is to use myoDN as an effective nucleic acid drug for muscle wastage related to different diseases.