Proteomic Profiling of Human Skeletal Muscle in Health and Disease

  • Paul R. Langlais
  • Lawrence J. MandarinoEmail author
Part of the Methods in Physiology book series (METHPHYS)


Skeletal muscle is the largest organ in the body by mass [1] and as such can affect many processes in addition to its obvious roles in locomotion and breathing. In these roles, diseases of skeletal muscle can have profound effects on human health. Because it also is sensitive to the effect of insulin to enhance glucose uptake, storage, and metabolism, it also is a key organ in insulin resistance and deranged glucose metabolism in obesity and type 2 diabetes mellitus [2], one of the most common chronic diseases in the world. The complex polygenic nature of this disease, reaching the limits of predictive power of knowledge gained by genome-wide association studies [3], and the profound genotype/environment interaction required to develop type 2 diabetes mellitus compel additional approaches to understanding pathogenesis of the disease. These approaches by necessity, therefore, must be able to deal with complexities of biological changes in tissues. Proteomics offers investigators such an approach. Skeletal muscle is the largest single contributor when insulin stimulates clearance of glucose from the blood in humans [4] and is one of the major regulators of body amino acid metabolism [5]. Because of these and other vitally important functions, human skeletal muscle has been a widely studied organ, with nearly 20,000 citations in PubMed as of June 2018. Moreover, although not as accessible as blood, skeletal muscle can be sampled readily by the use of percutaneous needle biopsies taken under local anesthesia. Because of the low rate of adverse events during these procedures and the lack of lasting effects [6], muscle biopsies can readily and ethically be performed not only in patients in need of diagnosis of disease but also in healthy control volunteers. This chapter will focus on studies of human skeletal muscle using mass spectrometry-based proteomics technologies. The primary focus will be on studies using biopsies to obtain skeletal muscle, but with selected references to studies using in vitro primary cultures of human myoblasts or differentiated myotubes. This chapter is not intended to be exhaustive, but rather to represent the array of areas which have proven to be amenable to mass spectrometry-based proteomics analysis in humans and for which such analyses have contributed in a major way to our base of knowledge.



The authors greatly acknowledge the artistic expertise of Marv Ruona. This work was supported in part by R01DK047936 (LJM), R01DK066483 (LJM), and R01DK098493 (PRL).


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© The American Physiological Society 2019

Authors and Affiliations

  1. 1.Division of Endocrinology, Department of Medicine, Center for Disparities in Diabetes, Obesity, and MetabolismCollege of Medicine, University of Arizona Health Sciences, The University of ArizonaTucsonUSA

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