Figure 2.

Intracellular formation of AGEs. During hyperglycemia, enhanced glucose flux through glycolysis induces the generation of superoxide anion by the mitochondria. Poly (ADP- ribose) polymerase (PARP) that protects DNA from cleavage induces a posttranslational modification of the glyceraldehyde 3P-dehydrogenase (GADPH) impairing glycolysis. Substrate (glyceraldehyde 3 phosphate and dihydroxyacetone phosphate) deviation leads to the generation of methylglyoxal that induces the formation of AGEs. Moreover, inflammation, fatty acid, amino acid, and ketone body oxidation generate oxoaldehydes, including glyoxal and glycolaldehyde that promote AGE generation. Oxidative stress increases by AGEs and by other biochemical pathways elicited by hyperglycemia (hexosamine, polyol, and protein kinase C). This vicious circle feeds the formation of AGEs and oxidative stress that is the base of cellular complications in diabetes mellitus. Parts of the figure were drawn using Servier Medical Art (https://smart.servier.com/, accessed on 14 December 2021).