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.

Skeletal muscle in the fight against chronic diseases

“…Skeletal muscles are divided into type I (slow‐twitch) and type II (fast‐twitch) fibres and can provide either short‐term maximum strength or endurance over long time periods . Skeletal muscle represents the primary tissue that is responsible for postprandial glucose processing . In addition to its role in locomotion, skeletal muscles are also fundamental for whole‐body metabolic health.…”

“…Myokines are part of a complex network and can either act locally or on other organs, such as liver, adipose tissue, brain and pancreas . Synthesis and release of myokines are regulated by differentiation, induction of insulin resistance or exercise …”

“…The expression of myokines after exercise is enhanced . Circulating IL‐6 is for example increased following exercise due to increases in skeletal muscle IL‐6 synthesis and secretion . Very likely, the contractile activity of a skeletal muscle influences its secretory function.…”

“…A reduced response of skeletal muscle tissue to insulin, called insulin resistance, is likely the primary defect leading to development of type 2 diabetes . In a second step, progressive β‐cell failure occurs and type 2 diabetes develops .…”

“…In parallel, they also showed differences in the secretory profile compared to non‐diabetic subjects; for example, the amounts of IL‐6, IL‐8 and TNF‐α were increased. This leads to the suggestion that the altered secretion of a number of myokines in patients plays a role in the response of skeletal muscle to type 2 diabetes …”