Proteomics of Skeletal Muscle: Focus on Insulin Resistance and Exercise Biology

Abstract

Skeletal muscle is the largest tissue in the human body and plays an important role in locomotion and whole body metabolism. It accounts for ~80% of insulin stimulated glucose disposal. Skeletal muscle insulin resistance, a primary feature of Type 2 diabetes, is caused by a decreased ability of muscle to respond to circulating insulin. Physical exercise improves insulin sensitivity and whole body metabolism and remains one of the most promising interventions for the prevention of Type 2 diabetes. Insulin resistance and exercise adaptations in skeletal muscle might be a cause, or consequence, of altered protein expressions profiles and/or their posttranslational modifications (PTMs). Mass spectrometry (MS)-based proteomics offer enormous promise for investigating the molecular mechanisms underlying skeletal muscle insulin resistance and exercise-induced adaptation; however, skeletal muscle proteomics are challenging. This review describes the technical limitations of skeletal muscle proteomics as well as emerging developments in proteomics workflow with respect to samples preparation, liquid chromatography (LC), MS and computational analysis. These technologies have not yet been fully exploited in the field of skeletal muscle proteomics. Future studies that involve state-of-the-art proteomics technology will broaden our understanding of exercise-induced adaptations as well as molecular pathogenesis of insulin resistance. This could lead to the identification of new therapeutic targets.

A Compact Quadrupole-Orbitrap Mass Spectrometer with FAIMS Interface Improves Proteome Coverage in Short LC Gradients

“…Combining the DDA analyzes with and without FAIMS slightly improves the depth of the library on both peptide and protein level. The observed discrepancy in identifications likely reflects the differences in protein expression levels across different organ proteomes, where highly abundant contractile proteins such as myosin dramatically increases the dynamic range of the expressed muscle proteome 22 . This high-quality dataset representing 213,000 unique peptides covering 12,909 protein-coding genes should represent a resource for the proteomics community, which can be bioinformatically mined or used as a general rodent spectral library for future DIA experiments.…”

Does obesity cause type 2 diabetes mellitus (T2DM)? Or is it the opposite?

“…Under euglycemic hyperinsulinemic conditions, 80% of glucose uptake occurs in skeletal muscle. 33 Studies using the euglycemic hyperinsulinemic clamp and femoral artery/vein catheterization to quantitate glucose uptake have allowed investigators to quantify leg muscle glucose uptake. Because adipose tissue uses 5% of an infused glucose load and bone is metabolically inert, the great majority of leg glucose uptake is accounted for by skeletal muscle.…”

“…Skeletal muscle is the major site of glucose uptake in the postprandial state in humans. Under euglycemic hyperinsulinemic conditions, 80% of glucose uptake occurs in skeletal muscle . Studies using the euglycemic hyperinsulinemic clamp and femoral artery/vein catheterization to quantitate glucose uptake have allowed investigators to quantify leg muscle glucose uptake.…”

RNA-sequencing analysis reveals the potential contribution of lncRNAs in palmitic acid-induced insulin resistance of skeletal muscle cells

“…Satellite cells [47], adult stem cells [47], macrophages [48], and vascular endothelial cells [49] reside in the skeletal muscle that possesses a three-dimensional microenvironment. Additionally, skeletal muscle fibers can be classified as fast oxidative-glycolytic, fast glycolytic, slow oxidative as well as various hybrid muscle fibers based on myosin heavy-chain (MHC) isoforms [50]. Different skeletal muscle fibers possess different metabolic properties [50].…”

“…Additionally, skeletal muscle fibers can be classified as fast oxidative-glycolytic, fast glycolytic, slow oxidative as well as various hybrid muscle fibers based on myosin heavy-chain (MHC) isoforms [50]. Different skeletal muscle fibers possess different metabolic properties [50]. The relatively low overlapping may also result from Based on functional enrichment analysis of differentially regulated mRNAs, these GO terms as shown in Figure 2A were in line with previous reports that the impaired fatty acid oxidation or lipid oxidation capacity could induce ectopic lipid accumulation in skeletal muscle cells [51] or tissues [52,53], which strongly accelerates IR.…”