title: Glucose: a vital toxin and potential utility of melatonin in protecting against the diabetic state.
abstract: The molecular mechanisms including elevated oxidative and nitrosative reactants, activation of pro-inflammatory transcription factors and subsequent inflammation appear as a unified pathway leading to metabolic deterioration resulting from hyperglycemia, dyslipidemia, and insulin resistance. Consistent evidence reveals that chronically-elevated blood glucose initiates a harmful series of processes in which toxic reactive species play crucial roles. As a consequence, the resulting nitro-oxidative stress harms virtually all biomolecules including lipids, proteins and DNA leading to severely compromised metabolic activity. Melatonin is a multifunctional indoleamine which counteracts several pathophysiologic steps and displays significant beneficial effects against hyperglycemia-induced cellular toxicity. Melatonin has the capability of scavenging both oxygen and nitrogen-based reactants and blocking transcriptional factors which induce pro-inflammatory cytokines. These functions contribute to melatonin's antioxidative, anti-inflammatory and possibly epigenetic regulatory properties. Additionally, melatonin restores adipocyte glucose transporter-4 loss and eases the effects of insulin resistance associated with the type 2 diabetic state and may also assist in the regulation of body weight in these patients. Current knowledge suggests the clinical use of this non-toxic indoleamine in conjunction with other treatments for inhibition of the negative consequences of hyperglycemia for reducing insulin resistance and for regulating the diabetic state.
authors.affiliation: Department of Physiology, School of Medicine, Gulhane Military Medical Academy, Ankara, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Korkmaz
authors.forename: Shuran
authors.initials: S
authors.lastname: Ma
authors.forename: Turgut
authors.initials: T
authors.lastname: Topal
authors.forename: Sergio
authors.initials: S
authors.lastname: Rosales-Corral
authors.forename: Dun-Xian
authors.initials: DX
authors.lastname: Tan
authors.forename: Russel J
authors.initials: RJ
authors.lastname: Reiter
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008550:Melatonin / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D026361:Reactive Nitrogen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D008550:Melatonin