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Reactive metabolites and antioxidant gene polymorphisms in type 2 diabetes mellitus

Monisha Banerjee1, Pushpank Vats1

  • 1Department of Zoology, Molecular and Human Genetics Laboratory, University of Lucknow, Lucknow, Uttar Pradesh, India.

Indian Journal of Human Genetics
|June 25, 2014
PubMed

Insights

Type 2 diabetes (T2DM) arises from insulin receptor (IR) dysfunction and oxidative stress caused by reactive metabolites (RMs). Low antioxidant enzyme levels exacerbate RM production, leading to IR and T2DM.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Background:

  • Type 2 diabetes mellitus (T2DM) is a complex syndrome stemming from insulin receptor (IR) dysfunction.
  • Oxidative stress, driven by reactive metabolites (RMs), plays a critical role in T2DM pathogenesis.
  • Key cellular enzymes contribute to RM production, including NADPH oxidase and eNOS.

Purpose of the Study:

  • To review the intricate roles of reactive metabolites (RMs) and antioxidant enzymes in the oxidative stress underlying T2DM.
  • To elucidate the molecular mechanisms linking RMs to glucose-mediated vascular damage.
  • To explore the impact of antioxidant enzyme polymorphisms on T2DM development.

Main Methods:

  • Literature review focusing on oxidative stress, reactive metabolites, and antioxidant enzymes in T2DM.
  • Analysis of molecular mechanisms including polyol pathway, AGEs, PKC, and hexosamine pathway.
  • Examination of the role of antioxidant enzymes like SOD, catalase, and glutathione peroxidase.

Main Results:

  • Excessive RMs, resulting from impaired antioxidant defenses, trigger stress pathways.
  • Specific RM-related pathways (polyol, AGEs, PKC, hexosamine) contribute to vascular damage in T2DM.
  • Functional polymorphisms in antioxidant enzymes are implicated in T2DM pathogenesis.

Conclusions:

  • Dysfunctional antioxidant enzymes and subsequent RM accumulation are central to T2DM development.
  • Targeting oxidative stress pathways may offer therapeutic strategies for T2DM.
  • Understanding the interplay between RMs and antioxidant enzymes is crucial for T2DM research.
Keywords:
Antioxidantsoxidative stresspolymorphismsreactive metabolitestype 2 diabetes mellitus

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