The Whole-transcriptome Landscape of Diabetes-related Sarcopenia Reveals the Specific Function of Novel lncRNA Gm20743

Background: Type 2 diabetes mellitus (T2DM) has been shown to increase the risk of sarcopenia that is characterized by decreased muscle mass, strength and function. While the exact mechanism remains unclear. Methods: Whole-transcriptome RNA sequencing was performed on the gastrocnemius (GAS) from the overt diabetes-induced sarcopenia model of db/db mice. Subsequently, differential expression and functional prediction analysis was performed to explore the gene-regulatory circuits in the pathogenesis of diabetes-induced sarcopenia. The RNA-seq data were verified in the GAS tissue of db/db mice and C2C12 myotubes exposed to palmitic acid by quantitative real-time polymerase chain reaction. Results: Thousands of differentially expressed genes were found in the skeletal muscle of db/db mice. RNA-seq data and informatics revealed the key lncRNA-mRNA and competing endogenous RNA interactions and indicated that a potential regulatory role of lncRNAs may be involved in oxidative phosphorylation, muscle contraction, glutathione metabolism and metabolic pathways in diabetes-induced sarcopenia. In addition,We characterized three core candidate lncRNAs Gm20743, Gm35438, 1700047G03Rik, and their potential function. Furthermore, the results suggested lncRNA Gm20743 may be involved in regulating mitochondrial function, oxidative stress, cell proliferation, and myotube differentiation in skeletal muscle cells. Conclusion: These findings improve our understanding of lncRNAs that may mediate muscle mass, strength and function in diabetes and represent potential therapeutic targets to diabetes-induced sarcopenia.