The cellular signalling mediated by exosomes: a new paradigm in the control of mitochondrial function and insulin response in primary skeletal muscle cells

Abstract

The exosomes have attracted much interest from the biomedical research community because of their multi potential function, such as sources of biomarkers for diseases, therapeutic agents or vehicles for drug delivery. It is believed that they have the capacity to carry proteins and nucleic acids that reflect their cell sources and could be internalized into other cells as a form of intercellular communication. The exosomes are a class of lipid vesicles (40-100nm) secreted by a diversity of cell types, which also include microvesicles, ectosomes, membrane particles, or apoptotic bodies. They are presently the most defined class among several classes of secreted membrane vesicles. Recent study has been shown that C2C12 release a great number of miokines (~400) identified by proteomic analysis. Also, the C2C12 myotube secreted exosomes reduce myoblast proliferation and induce differentiation. Another study showed that the contraction-induced skeletal muscle release higher amounts of microRNA-486. Interesting, the microRNA-486 decrease the gene expression of PTEN (protein able to decrease the PI3K/Akt insulin signaling pathway). Therefore, whether contraction-induced skeletal muscle release exosomes and that these vesicles may modulate the biological activity of C2C12 cell culture, is possible that intercellular communication mediated by exosomes could promote the transfer of signaling proteins related to mitochondrial biogenesis, and consequently improve the glucose uptake in insulin resistance skeletal muscle cells. . In this way, the aim of this study is to analyze whether the skeletal muscle treated with AICAR could release exosomes able to transfer the signaling proteins to improve the mitochondrial biogenesis and glucose uptake in insulin resistance skeletal muscle cells. Also, the study will investigate whether the overexpression or silencing of the identified exosomes proteins could improve or reduce respectively the oxygen consumption, glucose uptake and mitochondrial biogenesis in insulin resistance skeletal muscle cells. (AU)