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: Ahmet Korkmaz, Shuran Ma, Turgut Topal, Sergio Rosales-Corral, Dun-Xian Tan, Russel J Reiter
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 349 Issue 2 Pg. 128-37 (Feb 26 2012) ISSN: 1872-8057 [Electronic] Ireland
• PMID: 22079284 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Blood Glucose
• Glucose Transporter Type 4
• Insulin
• Reactive Nitrogen Species
• Reactive Oxygen Species
• Melatonin

Topics

• Adipocytes (metabolism, pathology)
• Animals
• Anti-Inflammatory Agents (metabolism, pharmacology)
• Antioxidants (metabolism, pharmacology)
• Blood Glucose (metabolism)
• Diabetes Mellitus, Type 2 (drug therapy, metabolism, physiopathology)
• Glucose Transporter Type 4 (metabolism)
• Glycosylation
• Humans
• Hyperglycemia (drug therapy, metabolism, physiopathology)
• Inflammation (drug therapy, metabolism, physiopathology)
• Insulin (metabolism)
• Insulin Resistance
• Melatonin (metabolism, pharmacology, therapeutic use)
• Oxidative Stress (drug effects)
• Reactive Nitrogen Species (antagonists & inhibitors, metabolism)
• Reactive Oxygen Species (antagonists & inhibitors, metabolism)
• Signal Transduction