ExoDia · Cross-talk between skeletal muscle and pancreatic islets: impact of exosomes

Cross-talk between skeletal muscle and pancreatic islets: impact of exosomes

The worldwide explosion of obesity has resulted in an ever-increasing prevalence of type 2 diabetes (T2D), a noncommunicable disease that affects more than 370 million people worldwide. T2D is characterized by insulin resistance with a relative deficiency in insulin secretion. It is now recognized that there is decreased beta-cell function and mass in T2D but the precise underlying mechanism remains to be determined. Skeletal muscle accounts for >50% of the total glucose uptake in the post-prandial state, it is also the largest organ in non-obese individuals. Recent studies demonstrated that there is conversation between skeletal muscle and beta-cells, and that certain peptides (i.e. myokines) secreted by insulin-resistant skeletal muscle cells may impact negatively on beta-cell function, proliferation and survival in T2D vs myokines from healthy skeletal muscle cells which have a protective role. Myokines can modulate the function and survival of pancreatic beta cells depending on its nature and metabolic status. Nevertheless, other factors than myokines could also be involved in this inter-organ communication. A novel concept suggests that extracellular vesicles (EVs), such as exosomes and microparticles, as a new cell-to-cell communication mode. Exosomes and microparticles are small vesicles (30-100 nm and 100-200 nm of diameter, respectively) that contain large amount of information (proteins, genetic material, lipids). We have demonstrated (Guay C, Cell Met 2019) that exosomes containing specific miRNA can target specifically beta-cells triggering chemokine expression and beta-cell death. Blocking those specific miRNA transferred in β cells decreases diabetes incidence in a diabetic mouse model. A major goal of this study is to provide further insight into the regulation of exosome secretion produced myotubes with different fiber composition (type I vs type II) and different insulin sensitivity, on the regulation of beta cell and islet function, with particular attention given to microRNA transfer from skeletal muscle cells to pancreatic beta cell and islet. The findings may have important implications for understanding decreased functional beta-cell mass in diabetes, especially in T2D etiology, and therefore bring new insights into the development of innovative therapies.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз