title: Methylglyoxal in Metabolic Disorders: Facts, Myths, and Promises.
abstract: Glucose and fructose metabolism originates the highly reactive byproduct methylglyoxal (MG), which is a strong precursor of advanced glycation end products (AGE). The MG has been implicated in classical diabetic complications such as retinopathy, nephropathy, and neuropathy, but has also been recently associated with cardiovascular diseases and central nervous system disorders such as cerebrovascular diseases and dementia. Recent studies even suggested its involvement in insulin resistance and beta-cell dysfunction, contributing to the early development of type 2 diabetes and creating a vicious circle between glycation and hyperglycemia. Despite several drugs and natural compounds have been identified in the last years in order to scavenge MG and inhibit AGE formation, we are still far from having an effective strategy to prevent MG-induced mechanisms. This review summarizes the endogenous and exogenous sources of MG, also addressing the current controversy about the importance of exogenous MG sources. The mechanisms by which MG changes cell behavior and its involvement in type 2 diabetes development and complications and the pathophysiological implication are also summarized. Particular emphasis will be given to pathophysiological relevance of studies using higher MG doses, which may have produced biased results. Finally, we also overview the current knowledge about detoxification strategies, including modulation of endogenous enzymatic systems and exogenous compounds able to inhibit MG effects on biological systems.
authors.affiliation: Laboratory of Physiology, Institute of Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, 3000-548, Coimbra, Portugal.|Department of Complementary Sciences, Coimbra Health School (ESTeSC), Instituto Politécnico de Coimbra, 3045-601, Coimbra, Portugal.
authors.forename: Paulo
authors.initials: P
authors.lastname: Matafome
authors.affiliation: Laboratory of Physiology, Institute of Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, 3000-548, Coimbra, Portugal.
authors.forename: Tiago
authors.initials: T
authors.lastname: Rodrigues
authors.affiliation: Laboratory of Physiology, Institute of Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, 3000-548, Coimbra, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sena
authors.affiliation: Laboratory of Physiology, Institute of Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, 3000-548, Coimbra, Portugal.
authors.forename: Raquel
authors.initials: R
authors.lastname: Seiça
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D011765:Pyruvaldehyde / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D017127:Glycation End Products, Advanced; D011765:Pyruvaldehyde
keywords: Diabetes; Endogenous and exogenous sources; Insulin resistance; Methylglyoxal; Obesity