IRS1 and diabetes mellitus: Next, we hypothesized that a blockade downstream of Akt might cause features resembling a T2DM-like syndrome in MuRF1- or MuRF2-KO mice, despite a continuously nonphysiologically augmented Akt activation (similar perhaps to a reported T2DM model where diabetes developed after insulin/lipid infusion by metabolic feedback in the presence of intact IRS-1, Akt, and AS160 signaling, as described by Hoy et al. [38]).