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. Author manuscript; available in PMC: 2013 Nov 1.
Published in final edited form as: Vascul Pharmacol. 2012 Jun 29;57(5-6):160–167. doi: 10.1016/j.vph.2012.06.004

Figure 1. RAGE – right in the middle of a vicious cycle of glycation and inflammation – potential links to diabetic complications.

Figure 1

In hyperglycemia characteristic of types 1 and 2 diabetes, a major result is excess production of methylglyoxal (MG). MG, through a series of subsequent reactions, may form the irreversible AGEs. When AGEs bind to their chief cell surface signaling receptor, a diverse set of consequences ensues – generation of oxidative stress, vascular dysfunction and inflammation – all of which synergize to trigger diabetic complications. The surprising finding that AGE levels were lower in hyperglycemic RAGE null mice led to the observation that RAGE downregulates Glo1, the chief enzyme responsible to detoxify MG. Hence, RAGE action contributes to AGE action, but, also to the perpetuation of AGE generation. We propose that a vicious cycle of AGE-RAGE stress is a key inciting factor in diabetes complications.