Original Article Methylglyoxal Impairs the Insulin Signaling Pathways Independently of the Formation of Intracellular Reactive Oxygen Species

Nonenzymatic glycation is increased in diabetes and leads to elevated levels of advanced glycation end products (AGEs), which link hyperglycemia to the induction of insulin resistance. In hyperglycemic conditions, intracellu-larly formed -ketoaldehydes, such as methylglyoxal, are an essential source of intracellular AGEs, and the abnor-mal accumulation of methylglyoxal is related to the devel-opment of diabetes complications in various tissues and organs. We have previously shown in skeletal muscle that AGEs induce insulin resistance at the level of metabolic responses. Therefore, it was important to extend our work to intermediates of the biosynthetic pathway leading to AGEs. Hence, we asked the question whether the reactive -ketoaldehyde methylglyoxal has deleterious effects on insulin action similar to AGEs. We analyzed the impact o