Interestingly, this gene is known to be an important mitochondrial factor8. and osteoprotegerin are triceps specific myokines with beta-cell protecting actions against proinflammatory cytokines. These results suggest that type I and type II muscle tissue could effect insulin secretion and beta-cell mass differentially in type 2 diabetes through specific myokines secretion. Intro Type 2 diabetes has a complex pathophysiology implicating several organs such as the adipose cells, the liver, muscle tissue and the pancreas. However, pancreatic beta-cells and the skeletal muscle mass can be considered like a central hinge of this disease. The muscle-pancreas axis was explained for the first time by our group in 20111. In this study, we founded a model in which main beta-cells were treated with conditioned medium prepared from human being main myotubes from vastus lateralis biopsies. We reported that human being skeletal muscle mass cells create and launch myokines depending on their state of insulin level of N-563 sensitivity, with bimodal action depending on insulin resistance of the skeletal muscle mass cells used to condition tradition medium1,2. However, although all skeletal muscle tissue share the same contractile function, they cannot be considered a homogenous organ from a metabolic perspective. The body consists of about 600 skeletal muscle tissue, which can be classified in three main organizations. Type I muscle tissue (e.g. soleus) are primarily composed of type I materials that are characterized by a sluggish ATP consumption rate and an oxidative rate of metabolism able to generate enough ATP to protect energy needs during a long exercise3. Type II muscle tissue (e.g. triceps brachii) are primarily composed of type II materials and are highly fatigable. Type II materials have a rate limiting step of glycolytic rate of metabolism and therefore cannot generate enough ATP to protect the high ATP consuming rate of myosin weighty chain II during exercise of long duration3. The last group is composed of muscle tissue containing an approximately equivalent amount of type I and type II materials (e.g. vastus lateralis)4. In the present work, we have established human models of skeletal muscle mass cells isolated from type I and type II muscle tissue and study their level of sensitivity to TNF-alpha induced insulin resistance. We have then investigated how the muscle mass type influences the profile of myokines secretion and their impact on beta-cells in order to determine fresh myokines implicated in dietary fiber type specific muscle mass pancreas crosstalk. We display here for the first time, that skeletal muscle mass cells from biopsies with different fiber type composition present a unique gene manifestation and myokine signature. Moreover, the effect of human being skeletal muscle mass cells on N-563 pancreatic beta-cells is definitely fiber type specific, with both positive and negative effects depending on the level of insulin level of sensitivity. Finally we display that ICAM2 angiogenin (ANG) and osteoprotegerin (OPG) are triceps specific myokines that reduce apoptosis of beta-cells. These 2 myokines also prevent the apoptosis induced either by pro-inflammatory cytokines (cytomix: TNF-alpha, INFgamma and IL-1beta) or the bad effect of insulin resistant conditioned medium from soleus skeletal muscle mass cells (TNF-S-CM). Morevover, OPG counteracts both the cytomix and TNF-S-CM negative effects on main pancreatic beta-cells proliferation and insulin secretion. Results RNA sequencing (RNA-seq) approach reveals a unique signature in cells isolated from soleus and triceps biopsies In order to characterize the transcriptomes of biopsies and main N-563 differentiated myotubes from soleus, triceps and vastus muscle mass, we founded gene manifestation profiles using RNA-seq. The correlation of the overall gene manifestation within biopsies or myotubes is very high (spearman rho ~0.9) whereas it drops when comparing the biopsies with the myotubes (spearman rho ~0.5) (Supplementary Fig.?1). A principal component analysis (PCA) on RPKM ideals segregates well the biopsies from your differentiated myotubes (Fig.?1A, Personal computer1). The soleus and the triceps biopsies form two unique clusters while the vastus is definitely more spread. N-563 This probably displays the heterogeneous structure of this muscle mass type composed of both type I and II materials (Supplementary Fig.?2, Personal computer1 and Personal N-563 computer2). The separation between the soleus and the triceps in induced myotubes is definitely less evident probably because of the incomplete differentiation of the cultured cells (Supplementary Fig.?3). The assessment between induced myotubes MC-S and MC-T shows 2935 differentially indicated genes that hit gene ontology terms and KEGG pathways such as extracellular region, developmental process, focal adhesion and cytokine-cytokine receptor. However, 864 genes are differentially indicated both in the biopsies and in the myotubes (Fig.?1B). The gene ontology analysis.