Less sweet!
Low glucose levels have been called an assistant in muscle recovery
Maria Azarova, Naked Science
Japanese scientists have found that, contrary to popular belief, satellite cells of skeletal muscles multiply faster in environments with low glucose levels. Previously, it was believed that mammalian cells feel better when, on the contrary, they receive more of this nutrient.
Skeletal muscles consist of striated muscle tissue, which contracts under the influence of nerve impulses, and have the ability to recover from injuries. The main participants in muscle regeneration are their specific stem cells, known as satellite cells, located between the sarcolemma – the cell membrane of a muscle cell or muscle fiber – and the basal plate of myofibrils, the organelles of striated muscle cells that ensure their contraction. Satellite cells are usually immobile and have a low metabolic rate, but they are the ones that trigger the myogenic program in response to muscle damage.
In the active state, these cells express myoblast determination protein 1 (MyoD) – a key transcription factor in myogenesis – and proliferate as myoblasts before differentiation and fusion to repair damaged muscles. The ability of satellite cells to regenerate muscles is also crucial for maintaining muscle mass. Since they are used in regenerative medicine, it is important to understand the mechanism underlying the behavior of such cells.
Glucose, in turn, is an important energy substrate and an anabolic precursor of various mammalian cells. In anaerobic glycolysis, two ATP molecules (adenosine triphosphate) are generated from one glucose molecule, and the central metabolite pyruvate plays the role of a nutrient medium in the mitochondrial tricarboxylic acid cycle through oxidative phosphorylation. Glucose is also needed for the synthesis of nucleotides via the pentose phosphate pathway, which is necessary in the production of ribose for DNA synthesis during cell division. Proliferating cells, such as cancer cells, prefer glucose as fuel for rapid proliferation. Therefore, it is believed that the media of various cultured cells need high concentrations of glucose to improve proliferation – tissue proliferation by cell division.
Media with a high glucose content are also used for the cultivation of muscle cells. However, scientists from Tokyo Metropolitan University found out that such conditions, on the contrary, are not suitable for growing satellite cells: they need an environment with a low glucose content. This contradicts the popular belief that mammalian cells feel better by getting more sugar to fuel activity. The study was published in the journal Frontiers in Cell and Developmental Biology (Furuichi et al., Excess Glucose Impedes the Proliferation of Skeletal Muscle Satellite Cells Under Adhered Culture Conditions).
A scientific group led by Yasuro Furuichi, Yasuko Manabe and Nobuharu L. Fujii studied how satellite cells of skeletal muscles develop outside the body – in Petri dishes. They noticed that higher glucose levels negatively affected their growth rate. A low-glucose environment resulted in more cells with all the biochemical markers needed for effective proliferation. In addition, the population of reserve cells increased due to a decrease in glucose concentration (this was indicated by the expression of a protein called Pax7, which plays a major role in muscle regeneration). High levels of this nutrient have been found to disrupt important functions of satellite cells, such as proliferation and self-renewal. Apparently, such excessive concentrations are a negative factor for skeletal muscle homeostasis, since hyperglycemia causes a violation of their regeneration and atrophy.
Scientists also managed to derive pure cultures of satellite cells - because an environment with an ultra–low glucose content does not allow other types of cells to multiply. This could be an incentive for other biomedical research. Meanwhile, during experiments with media with a high glucose content, satellite cell cultures turned into a mixture due to the fact that other cell types in the original sample also multiplied. By maintaining a low glucose level, the authors of the study were able to create conditions where satellites could multiply, but other types of cells could not.
The sugar levels used in previous experiments coincide with those observed in diabetic people. This may explain why such patients face loss of muscle mass. But how did biologists achieve such a low glucose level? To do this, they added glucose oxidase, an enzyme that digests glucose. Therefore, the cells lived surprisingly normally and developed well. Apparently, they receive energy from a completely different source, the scientists noted. And it will have to be determined in further studies.
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