Slc2a6 regulates myoblast differentiation by targeting LDHB

Abstract

Background Type 2 diabetes mellitus is a global health problem. It often leads to a decline in the differentiation capacity of myoblasts and progressive loss of muscle mass, which in turn results in deterioration of skeletal muscle function. However, effective therapies against skeletal muscle diseases are unavailable. Methods Skeletal muscle mass and differentiation ability were determined in db/+ and db/db mice. Transcriptomics and metabolomics approaches were used to explore the genetic mechanism regulating myoblast differentiation in C2C12 myoblasts. Results In this study, the relatively uncharacterized solute carrier family gene Slc2a6 was found significantly up-regulated during myogenic differentiation and down-regulated during diabetes-induced muscle atrophy. Moreover, RNAi of Slc2a6 impaired the differentiation and myotube formation of C2C12 myoblasts. Both metabolomics and RNA-seq analyses showed that the significantly differentially expressed genes (e.g., LDHB) and metabolites (e.g., Lactate) during the myogenic differentiation of C2C12 myoblasts post-Slc2a6-RNAi were enriched in the glycolysis pathway. Furthermore, we show that Slc2a6 regulates the myogenic differentiation of C2C12 myoblasts partly through the glycolysis pathway by targeting LDHB, which affects lactic acid accumulation. Conclusion Our study broadens the understanding of myogenic differentiation and offers the Slc2a6-LDHB axis as a potential therapeutic target for the treatment of diabetes-associated muscle atrophy.

Muscle-Specific Ablation of Glucose Transporter 1 (GLUT1) Does Not Impair Basal or Overload-Stimulated Skeletal Muscle Glucose Uptake

“…It is also possible that each transporter could be expressed in one or more distinct cell types found within overload-stimulated muscle tissue. For example, while GLUT1 has been detected in myocytes and endothelial cells [ 34 , 35 , 36 , 37 , 38 ]; GLUT3 has been detected in myocytes and neurons [ 52 , 53 ]; GLUT6 in myocytes, endothelial, and immune cells [ 54 , 55 , 56 ]; and GLUT10 in myocytes and vascular smooth muscle cells [ 53 , 57 ]. Prior work in rat muscle has demonstrated that 1 week of mechanical overload is sufficient to increase the capillary density to muscle fiber ratio [ 58 ]; providing a possible explanation for the induction of endothelial cell-derived GLUTs.…”

Pyruvate dehydrogenase B regulates myogenic differentiation via the FoxP1–Arih2 axis

“… 27 Our previous study also confirmed the detrimental effect of lactate accumulation on myogenic differentiation and the down‐regulation of PDHB expression during this process. 28 How PDHB regulates glycolysis and lactate production in the skeletal muscle needs further study.…”