MDM2 and Hyperglycemia: One potential mechanism for the decrease in STUB1 is based upon a previous report demonstrating that stress due to hyperglycemia decreases the ubiquitin E3 ligase activity of Mdm2 by inducing the phosphorylation of this residue in RINm5F cells37; therefore, it is likely that hyperglycemia due to insulin resistance may cause lower levels of STUB1 in T2D.