Science & Technology

Reduce sugar!New studies show that hypoglycemic levels may help muscle repair

image: Lowering glucose levels promotes cell proliferation of muscle stem cells, suggesting that excess glucose interferes with cell proliferation capacity.
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Credit: Tokyo Metropolitan University

Researchers at Tokyo, Japan-Tokyo Metropolitan University have shown that skeletal muscle satellite cells, a major player in muscle repair, proliferate better in a low-glucose environment. This goes against the general wisdom that mammalian cells work better with more sugar that promotes their activity. Since other cell types cannot proliferate in an ultra-low glucose environment, the team can produce pure cultures of satellite cells, which can significantly boost biomedical research.

Healthy muscles are an important part of a healthy life. With daily use exhaustion, muscles are continually repaired and kept in top condition. In recent years, scientists have begun to understand how muscle repair works at the cellular level. Skeletal muscle satellite cells have proven to be of particular importance. It is a special type of stem cell that lies between the two layers of the sarcolemma and the basement membrane and wraps the myofibroblasts in individual myofibers. When myosatellite cells are damaged, the satellite cells overdrive, proliferate, and eventually fuse with the myosatellite cells. Not only does this help repair damage, it also maintains muscle mass. Understanding the specific mechanisms involved is an important medical challenge in understanding how muscle is lost due to illness, inactivity, or age.

A team of scientists at Tokyo Metropolitan University, led by Assistant Professor Yasuro Furuichi, Associate Professor Yasuko Manabe, and Professor Nobuharu Fujii, is studying how skeletal muscle satellite cells proliferate in vitro. Looking at the cells growing in the Petri dish of growth medium, they noticed that higher levels of glucose adversely affected the rate at which they grew. This is counterintuitive. Glucose is thought to be essential for cell growth. It is converted to ATP, a fuel that drives many cell activities. Nevertheless, the team confirmed that lower glucose medium led to more cells and that all biochemical markers expected higher cell proliferation.

They also confirmed that this was not the case for all cells. In experiments on high glucose medium, the culture of satellite cells was always terminated as a mixture, as other cell types of the original sample were also proliferating. Keeping blood glucose low can create a situation where satellite cells can proliferate but other cell types cannot, allowing for a very pure culture of skeletal muscle satellite cells. This is an important prerequisite for studying these cells in a variety of situations, including regenerative medicine. So was the amount of glucose in their first experiment somehow “just right”? The team added the glucose-digesting enzyme glucose oxidase to obtain lower levels of glucose and proliferated satellite cells in this glucose-depleted medium. Surprisingly, the cells appeared to be functioning well and proliferated normally. The bottom line is that these particular stem cells appear to draw their energy from completely different sources. Work is underway to determine what this is.

The team notes that the sugar content used in previous experiments was consistent with that seen in diabetics. This may explain why diabetics have loss of muscle mass and can have a significant impact on how they keep their muscles healthy longer.


This work was supported by the Grant-in-Aid for Scientific Research of the Japan Society for the Promotion of Science (18K19751, 20H04079, 17H02159, 18H04086), Sumitomo Dainippon Pharma Co., Ltd., and the Uehara Memorial Foundation.

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Reduce sugar!New studies show that hypoglycemic levels may help muscle repair Reduce sugar!New studies show that hypoglycemic levels may help muscle repair

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