VHL and Hyperglycemia: Additional mechanisms may also contribute to the repression of the HIF-1α-HRE pathway by hyperglycemia: for instance, methylglyoxal, a glycolytic metabolite which accumulates in cells exposed to HG concentrations, has been found to trigger PHD-pVHL-independent proteasomal degradation of HIF-1α35 and to decrease HIF-1α transcriptional activity by impairing HIF-1 binding to the coactivator p30029.