title: Altered Myokine Secretion Is an Intrinsic Property of Skeletal Muscle in Type 2 Diabetes.
abstract: Skeletal muscle secretes factors, termed myokines. We employed differentiated human skeletal muscle cells (hSMC) cultured from Type 2 diabetic (T2D) and non-diabetic (ND) subjects to investigate the impact of T2D on myokine secretion. Following 24 hours of culture concentrations of selected myokines were determined to range over 4 orders of magnitude. T2D hSMC released increased amounts of IL6, IL8, IL15, TNFa, Growth Related Oncogene (GRO)a, monocyte chemotactic protein (MCP)-1, and follistatin compared to ND myotubes. T2D and ND hSMC secreted similar levels of IL1ß and vascular endothelial growth factor (VEGF). Treatment with the inflammatory agents lipopolysaccharide (LPS) or palmitate augmented the secretion of many myokines including: GROa, IL6, IL8, IL15, and TNFa, but did not consistently alter the protein content and/or phosphorylation of IkBa, p44/42 MAPK, p38 MAPK, c-Jun N-terminal kinase (JNK) and NF-kB, nor lead to consistent changes in basal and insulin-stimulated glucose uptake or free fatty acid oxidation. Conversely, treatment with pioglitazone or oleate resulted in modest reductions in the secretion of several myokines. Our results demonstrate that altered secretion of a number of myokines is an intrinsic property of skeletal muscle in T2D, suggesting a putative role of myokines in the response of skeletal muscle to T2D.
authors.affiliation: Veterans Affairs San Diego Healthcare System, San Diego, CA, United States of America.|Department of Medicine, Division of Endocrinology & Metabolism, University of California San Diego, La Jolla, CA, United States of America.
authors.forename: Theodore P
authors.initials: TP
authors.lastname: Ciaraldi
authors.affiliation: Veterans Affairs San Diego Healthcare System, San Diego, CA, United States of America.|Department of Medicine, Division of Endocrinology & Metabolism, University of California San Diego, La Jolla, CA, United States of America.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Ryan
authors.affiliation: Veterans Affairs San Diego Healthcare System, San Diego, CA, United States of America.|Department of Medicine, Division of Endocrinology & Metabolism, University of California San Diego, La Jolla, CA, United States of America.
authors.forename: Sunder R
authors.initials: SR
authors.lastname: Mudaliar
authors.affiliation: Veterans Affairs San Diego Healthcare System, San Diego, CA, United States of America.|Department of Medicine, Division of Endocrinology & Metabolism, University of California San Diego, La Jolla, CA, United States of America.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Henry
mesh_terms: D015415:Biomarkers; D016022:Case-Control Studies; D002478:Cells, Cultured; D018925:Chemokines / Q000097:blood; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D018925:Chemokines; D017077:Culture Media, Conditioned; D016207:Cytokines; D005227:Fatty Acids; D018836:Inflammation Mediators; D005947:Glucose