Diabetes is linked to various health problems including a decline in muscle mass.
In a new study, researchers found that elevation of blood sugar levels leads to muscle atrophy and that two proteins, WWP1 and KLF15, play key roles in this phenomenon.
The research was conducted by a team at Kobe University.
Muscle mass decline linked to aging impairs our physical activity, making us susceptible to a variety of health problems and thus leading to shortened lifespans.
Age-dependent muscle mass decline and the consequent impairment of physical activity is known as “sarcopenia,” a serious health burden in aging societies.
Previous studies have found that patients with diabetes are prone to muscle loss as they age, but an underlining mechanism for this phenomenon remains unclear.
Diabetes is a disease caused by insufficient action of the hormone insulin.
Insulin not only lowers blood sugar levels but promotes the growth and proliferation of cells; insufficient action of insulin has been thought to result in the suppression of growth and proliferation of muscle cells, which in turn contribute to the decline in skeletal muscle mass.
In the study, the team made the surprising discovery that a rise in blood sugar levels triggers the decline in muscle mass, and they uncovered the important roles of two proteins in this phenomenon.
They found that the abundance of transcription factor KLF15 increased in skeletal muscle of diabetic mice, and mice that lack KLF15 specifically in muscle were resistant to diabetes-induced skeletal muscle mass decline.
These results indicate that diabetes-induced muscle loss is attributable to increased amounts of KLF15.
WWP1 is a member of proteins called ubiquitin ligase. Under normal conditions, WWP1 promotes the degradation of KLF15 protein.
When blood sugar levels rise, the amount of WWP1 decreases, which in turn decelerates the degradation of KLF15 and thus the increase in the cellular abundance of KLF15.
This study showed for the first time that elevation of blood sugar levels triggers muscle mass decline and that the two proteins WWP1 and KLF15 contribute to diabetes-induced muscle mass decline.
The team says if doctors can develop a drug that strengthens the function of WWP1 or weakens the function of KLF15, it would lead to a groundbreaking new treatment.
One author of the study is Professor Wataru Ogawa.
The study is published in JCI Insight.
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