REVIEW: Signaling and Gene Expression in Skeletal Muscles in Type 2 Diabetes: Current Results and OMICS Perspectives

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Alexander V. Vorotnikov^1,2,a*, Daniil V. Popov^1,3,b*, and Pavel A. Makhnovskii¹

¹Institute of Biomedical Problems, Russian Academy of Sciences, 123007 Moscow, Russia

²National Medical Research Center of Cardiology, Ministry of Healthcare of the Russian Federation, 121552 Moscow, Russia

³Faculty of Fundamental Medicine, Lomonosov Moscow State University, 119991 Moscow, Russia

^* To whom correspondence should be addressed.

Received May 10, 2022; Revised August 9, 2022; Accepted August 10, 2022

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Skeletal muscles mainly contribute to the emergence of insulin resistance, impaired glucose tolerance and the development of type 2 diabetes. Molecular mechanisms that regulate glucose uptake are diverse, including the insulin-dependent as most important, and others as also significant. They involve a wide range of proteins that control intracellular traffic and exposure of glucose transporters on the cell surface to create an extensive regulatory network. Here, we highlight advantages of the omics approaches to explore the insulin-regulated proteins and genes in human skeletal muscle with varying degrees of metabolic disorders. We discuss methodological aspects of the assessment of metabolic dysregulation and molecular responses of human skeletal muscle to insulin. The known molecular mechanisms of glucose uptake regulation and the first results of phosphoproteomic and transcriptomic studies are reviewed, which unveiled a large-scale array of insulin targets in muscle cells. They demonstrate that a clear depiction of changes that occur during metabolic dysfunction requires systemic and combined analysis at different levels of regulation, including signaling pathways, transcription factors, and gene expression. Such analysis seems promising to explore yet undescribed regulatory mechanisms of glucose uptake by skeletal muscle and identify the key regulators as potential therapeutic targets.

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KEY WORDS: skeletal muscle, insulin resistance, insulin signaling, AMPK, glucose uptake, phosphoproteome, transcriptome, type 2 diabetes

DOI: 10.1134/S0006297922090139

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