title: Reactive metabolites as a cause of late diabetic complications.
abstract: Patients suffering from DN (diabetic neuropathy) suffer from the coexistence of positive (i.e. pain, hypersensitivity, tingling, cramps, cold feet, etc.) and negative (i.e. loss of sensory perception, delayed wound healing, etc.) symptoms. Elevated blood glucose alone cannot explain the development and progression of DN. Recently it has been shown that the endogenous reactive metabolite MG (methylglyoxal), elevated as a consequence of reduced Glo1 (glyoxalase I), can contribute to the gain of function via post-translational modification of neuronal ion channels involved in chemosensing and action potential generation in nociceptive nerve endings. The effects of dicarbonyls on the neuronal compartment provides a unifying mechanism for the development of DN. Targeting the accumulation and effects of MG may therefore provide new, more effective, therapeutic approaches for the treatment of DN.
authors.affiliation: *Department of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, INF 410, 69120 Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fleming
authors.affiliation: *Department of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, INF 410, 69120 Heidelberg, Germany.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Nawroth
mesh_terms: D000818:Animals; D048909:Diabetes Complications / Q000209:etiology* / Q000378:metabolism*; D003929:Diabetic Neuropathies / Q000209:etiology / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000378:metabolism; D011765:Pyruvaldehyde / Q000378:metabolism; D012584:Sciatic Nerve / Q000378:metabolism / Q000473:pathology
chemical_list: D017127:Glycation End Products, Advanced; D011765:Pyruvaldehyde; D007791:Lactoylglutathione Lyase