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Diabetes mellitus is badociated with various health problems, including a decrease in skeletal muscle mbad. A research group led by Professor Wataru Ogawa of the Graduate School of Medicine at the University of Kobe revealed that elevated blood sugar levels resulted in muscle atrophy and that two proteins, WWP1 and KLF15, play a key role in this phenomenon. These results were published on February 21 in the online edition of JCI Insight.
The decline in muscle mbad badociated with aging alters our physical activity, making us vulnerable to a variety of health problems and leading to reduced life span. The decline in age-related muscle mbad and the resulting loss of physical activity are called "sarcopenia", a serious health problem in aging societies.
We already knew that patients with diabetes mellitus were subject to muscle loss as they aged, but the mechanism underlying this phenomenon remains unclear. Diabetes mellitus is a disease caused by insufficient action of the hormone insulin. Insulin not only lowers blood sugar but promotes cell growth and proliferation; Insufficient insulin action was thought to slow down the growth and proliferation of muscle cells, which in turn contributed to the decrease in skeletal muscle mbad.
Professor Ogawa's research team made the surprising discovery that an increase in blood sugar levels triggers the decline in muscle mbad and revealed the important role of two proteins in this phenomenon. They found that the abundance of transcription factor KLF15 increased in the skeletal muscle of diabetic mice and that mice lacking KLF15 specifically in muscle were resistant to the decline in skeletal muscle mbad induced by diabetes (Figure 1). . These results indicate that the muscle loss induced by diabetes is due to an increase in the amounts of KLF15.
The team investigated the mechanism for increasing the abundance of KLF15 in the skeletal muscle of diabetic mice. They found that elevated blood sugar levels slowed down the degradation of KLF15 protein, which resulted in an increase in the amount of this protein. Professor Ogawa's team has also discovered that a protein called WWP1 plays a key role in regulating the degradation of KLF15 protein.
WWP1 is a member of proteins called ubiquitin ligase. When a small protein called "ubiquitin" binds to other proteins, the degradation of ubiquitin-bound proteins is accelerated. Under normal conditions, WWP1 promotes degradation of KLF15 protein by binding ubiquitins to KLF15, thereby maintaining a low abundance of KLF15 in the cells. As blood glucose levels increase, the amount of WWP1 decreases, slowing the degradation of KLF15 and thus the increase in KLF15 cell abundance.
This study revealed for the first time that the rise in blood glucose triggers the decline of muscle mbad and that both proteins WWP1 and KLF15 contribute to the decline in muscle mbad induced by diabetes.
Besides diabetes mellitus, other problems, such as physical inactivity or aging, result in a loss of muscle mbad. KLF15 and WWP proteins, which have been shown to contribute to diabetes-induced muscle loss, may also be badociated with other causes of muscle loss. Currently, no medication is available for the treatment of muscle loss. Professor Ogawa comments, "If we develop a drug that enhances the function of WWP1 or weakens the function of KLF15, it will lead to a revolutionary new treatment."
Source:
http://www.kobe-u.ac.jp/research_at_kobe_en/NEWS/news/2019_02_22_01.html
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