Researchers have discovered the mechanism of how diabetes causes muscle loss

Diabetes is a metabolic disease characterized by hyperglycemia. Due to long-lasting hyperglycemia, diabetes causes chronic damage and dysfunction to various tissues, especially eyes, kidney, heart, blood vessels and nerves.

Diabetes is associated with a variety of health problems, including a decline in skeletal muscle mass. A research team at the Kobe University Graduate School of Medicine has found that elevated blood glucose levels can lead to muscle atrophy. And they also pointed out two proteins play an important role in the process. The findings were published in the online edition of JCI Insight on 21 February.

As the saying goes, a person's legs firstly become stiff before he gets old. It suggests that our muscle will decrease with age increases. Sarcopenia is the loss of muscle mass due to the natural aging process. Skeletal muscle provides powder for human movement system, so muscle aging and atrophy is an important sign of human aging. Sarcopenia is easy to cause fracture and joint injury, and it also affects organic function and may trigger heart and lung failure even death.

Muscle tissue is a very important tissue of the human body that uses blood glucose. Insulin is secreted from the pancreas into the bloodstream and then into different tissues, including muscle tissue. The muscle cells are filled with insulin sensors. Once the insulin molecules are combined with the sensors, the muscle cells will open the door, allowing blood glucose to enter the muscle cells smoothly, and the blood glucose can be fully utilized.

As we know, patients with diabetes are prone to muscle loss as they age, but the underlying mechanisms of this phenomenon remain unclear. Diabetes is a disease caused by insufficient action of insulin. Insulin can not only decrease blood glucose levels but also can promote the growth and proliferation of cells. It has been demonstrated that inadequate insulin action leads to inhibition of muscle cell growth and proliferation, which in turn results in a decline in skeletal muscle mass.

The research team found an increased abundance of the transcription factor KLF15 in skeletal muscle of diabetic mice, while muscle-deficient mice were resistant to diabetes-induced skeletal muscle degradation. These results indicate that increased KLF15 is responsible for diabetic muscle loss.

Next, the team further investigated the mechanism of increased KLF15 abundance in skeletal muscle of diabetic mice. They discovered that elevated blood glucose levels slowed the degradation of KLF15, thus causing an increase in the protein itself. And a protein called WWP1 plays a key role in regulating KLF15 degradation.

WWP1 is a member of a protein called ubiquitin-protein ligase. When a small protein called ubiquitin binds to other proteins, the degradation of the ubiquitin-binding protein is accelerated. Under normal conditions, WWP1 promotes KLF15 degradation by binding ubiquitin protein to KLF15, thus maintaining low cell KLF15 abundance. When the blood glucose level increases, the amount of WWP1 decreases, which in turn slows down the degradation of KLF15, thus increasing the cell abundance of KLF15.

The study is the first to show that elevated blood glucose levels trigger a decline in muscle mass and that two proteins, WWP1 and KLF15, cause a decline in muscle mass caused by diabetes.

At present, there are no drugs available to treat muscle loss. If a drug that enhances WWP1 or weakens KLF15 is developed, it could lead to a pioneering new treatment.