GDF15 Is a Contraction-Induced Myokine That Regulates Pancreatic ß-Cell Function

β-cell dysfunction plays a major role in the onset of type 2 diabetes (T2D). Exercise improves or restores β-cell function in both humans and rodents with T2D. The specific mechanism is unclear. We hypothesized that exercise-induced myokines engage in cross-talk with the pancreas to help regulate β-cell function and mass. To test our hypothesis, differentiated C2C12 myotubes were subjected to electrical pulse stimulation (EPS) to simulate in vivo exercise. EPS-conditioned media from the contracting myotubes significantly elevated glucose-stimulated insulin secretion (GSIS) in β-cells vs. non-EPS control conditions (P In summary, these findings expand our understanding of skeletal muscle as an endocrine organ and identify GDF15 as a potential myokine for T2D therapy. Disclosure H. Zhang: None. A. Mulya: None. S. Nieuwoudt: None. R. McDowell: None. J.P. Kirwan: None.