INSR and diabetes mellitus: Plakoglobin stabilizes these heteromultimers on the plasma membrane to maintain tissue integrity because its downregulation (by shJUP) in normal muscle reduced the membrane content of plakoglobin-DGC-insulin receptor co-assemblies and caused atrophy (Fig. 3), and increasing plakoglobin levels in fasting or diabetes stabilized these protein clusters on the muscle membrane and attenuated atrophy (Figs. 5 and 6e).