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.

Highlights

  • The prevalence of obesity and Type 2 diabetes is rising at an astronomical rate both in developed and developing countries

  • A more recent study showed that skeletal muscle from rodent model for diabetes bear increased mitochondrial protein degradation and decreased protein synthesis, resulting in reduced abundance of proteins involved in mitochondrial respiration and beta oxidation [69]

  • Type 2 diabetes is associated with impaired metabolic flexibility, i.e., inability to switch from fatty acid to glucose oxidation in response to insulin [84]

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Summary

Introduction

The prevalence of obesity and Type 2 diabetes is rising at an astronomical rate both in developed and developing countries. The pathogenesis of Type 2 diabetes involves functional defects in all major organs governing metabolic control including skeletal muscle, adipose tissue, and liver and pancreatic β-cells [1]. These defects lead to an impaired capacity of insulin to regulate whole body glucose homeostasis, a condition commonly known as “insulin resistance”. Because the majority of the cellular processes are controlled by proteins, proteomics technology offers enormous promise for investigating molecular mechanisms underlying skeletal muscle insulin resistance and exercise-induced adaptation. Comprehensive proteomics of complex samples such as tissues in general and skeletal muscle in particular is challenging [19]

Complexity of Skeletal Muscle Tissue
Deep Proteome of Skeletal
Emerging Technology for Skeletal Muscle Proteome
Sample Preparation
LCMS Instrumentations
Computational Proteomics
Proteome Profiling of Diabetic Skeletal Muscle
Diabetes and Skeletal Muscle PTMs
Diabetes and Muscle Strength
Skeletal Muscle Biomarkers for Diabetes
Interaction Proteomics
Proteomics Application to Study Exercise Biology
Exercise Training and Skeletal Muscle Adaptations
Secretome of Insulin Resistant and Exercised Skeletal Muscle
Conclusions
Findings
Methods
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