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Redox Biol. 2014;2:170-7. doi: 10.1016/j.redox.2013.12.001. Epub 2013 Dec 11.

Reactive metabolites and antioxidant gene polymorphisms in Type 2 diabetes mellitus.

Author information

1
Molecular & Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow 226007, India. Electronic address: mhglucknow@yahoo.com.
2
Molecular & Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow 226007, India. Electronic address: pushpank134@gmail.com.

Abstract

Type 2 diabetes mellitus (T2DM), by definition is a heterogeneous, multifactorial, polygenic syndrome which results from insulin receptor dysfunction. It is an outcome of oxidative stress caused by interactions of reactive metabolites (RMs) interactions with lipids, proteins and other mechanisms of human body. Production of RMs mainly superoxide (O2(-)) has been found in a variety of predominating cellular enzyme systems including NAD(P)H oxidase, xanthine oxidase (XO), cyclooxygenase (COX), uncoupled endothelial nitric oxide synthase (eNOS) and myeloperoxidase (MPO). The four main RM related molecular mechanisms are: increased polyol pathway flux; increased advanced glycation end-product (AGE) formation; activation of protein kinase C (PKC) isoforms and increased hexosamine pathway flux which have been implicated in glucose-mediated vascular damage. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), nitric oxide synthase (NOS) are antioxidant enzymes involved in scavenging RMs in normal individuals. Functional polymorphisms of these antioxidant enzymes have been reported to be involved in pathogenesis of T2DM individuals. The low levels of antioxidant enzymes or their non-functionality results in excessive RMs which initiate stress related pathways thereby leading to insulin resistance and T2DM. An attempt has been made to review the role of RMs and antioxidant enzymes in oxidative stress resulting in T2DM.

KEYWORDS:

Antioxidants; Oxidative stress; Polymorphisms; Reactive metabolites; Type 2 diabetes mellitus

PMID:
25460725
PMCID:
PMC4297945
DOI:
10.1016/j.redox.2013.12.001
[Indexed for MEDLINE]
Free PMC Article

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