Reactive metabolites and antioxidant gene polymorphisms in type 2 diabetes mellitus.
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Date
2014-01
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Abstract
Type 2 diabetes mellitus (T2DM), by definition is a
heterogeneous, multifactorial, polygenic syndrome which
results from insulin receptor (IR) dysfunction. It is an outcome of
oxidative stress caused by interactions of reactive metabolites
(RMs) with lipids, proteins and other molecules of the human
body. Production of RMs mainly superoxides (•O2
−) has been
found in a variety of predominating cellular enzyme systems
including nicotinamide adenine dinucleotide phosphate
oxidase, xanthine oxidase, cyclooxygenase, endothelial nitric
oxide synthase (eNOS) and myeloperoxidase. The four main
RM related molecular mechanisms are: increased polyol
pathway flux; increased advanced glycation end‑product
formation; activation of protein kinase C isoforms and increased
hexosamine pathway flux which have been implicated in
glucose‑mediated vascular damage. Superoxide dismutase,
catalase, glutathione peroxidase, glutathione‑S‑transferase
and NOS are antioxidant enzymes involved in scavenging
RMs in normal individuals. Functional polymorphisms of these
antioxidant enzymes have been reported to be involved in the
pathogenesis of T2DM. The low levels of antioxidant enzymes
or their non‑functionality results in excessive RMs which
initiates stress related pathways thereby leading to IR and
T2DM. An attempt has been made to review the role of RMs
and antioxidant enzymes in oxidative stress resulting in T2DM.
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Keywords
Antioxidants, oxidative stress, polymorphisms, reactive metabolites, type 2 diabetes mellitus
Citation
Banerjee Monisha, Vats Pushpank. Reactive metabolites and antioxidant gene polymorphisms in type 2 diabetes mellitus. Indian Journal of Human Genetics. 2014 Jan-Mar ;20 (1): 10-19.