EGF and Hyperglycemia: For example, in mesangial cells exposed to hyperglycemia, general inhibition of matrix metalloproteases, MMPs, (known to be involved in EGF-like ligand shedding) or specifically of HB-EGF ligand inhibited the activation of both, EGFR and downstream AKT signaling (Uttarwar et al., 2011; Uttarwar et al., 2012).