Beta-Cell Function and Survival Are Modulated Differentially by Type I or Type II Muscle through Specific Myokines

Type 2 diabetes has a complex pathophysiology implicating several organs as the adipose tissue the liver, the skeletal muscle and the pancreas. Tissue crosstalk is emerging as a determinant way to coordinate the different organs implicated in glucose homeostasis. Among the inter-organ communication factors, muscle-secreted myokines can modulate the function and survival of pancreatic beta-cells. We establish human primary in vitro models of cells isolated from soleus (type I), triceps brachii (type II) and vastus lateralis (mixte) muscles to study the myokines profile secretion using and antibody-based array, the transcriptome using RNA-sequencing, and their sensitivity to TNF-alpha-induced insulin resistance, by assessing the glucose uptake rate. We then investigate how the muscle type and insulin resistance status impact on beta-cell function (glucose stimulated insulin secretion), survival (proliferation and apoptose) in order to identify new myokines in fiber type specific muscle pancreas crosstalk. We show that type I and type II primary myotubes present specific mRNA and myokine signatures as well as different sensitivity to TNF-alpha induced insulin resistance (TNF-alpha failed to induce insulin resistance in type II muscle). We also report here that the impact of myokines on beta-cells proliferation, apoptosis and insulin secretion, depends on fiber types and their metabolic status. Finally, that angiogenin and osteoprotegerin are triceps specific myokines with beta-cell protective actions against proinflammatory cytokines. These results suggest that type I and II muscles could impact insulin secretion and beta-cell mass differentially in type 2 diabetes through specific myokines secretion. Disclosure M.L. Mizgier: None. S. Rutti: None. M. Pinget: None. K. Bouzakri: None.