Molecular Mechanisms Linking Oxidative Stress and Diabetes Mellitus

Table 2

Main molecular mechanisms by which oxidative stress induces insulin resistance.

Molecular mechanisms	Effects	Ref.
β-Cell dysfunction	Induces beta-cell dysfunction through various molecular pathways such as apoptotic events, impairing KATP channels, inhibiting transcription factors as Pdx-1 and MafA, suppressing β-cell neogenesis, and inducing mitochondrial dysfunction in beta cells	[48, 55–62, 71, 72]
GLUT-4 expression and/or localization	Suppresses transcriptional factors involved in GLUT-4 expression as PPAR-γ, CEB/Ps, nuclear factor-1, p85, HIF-1α, MEF2, and Nf-κb; suppresses micro RNAs involved in GLUT-4 expression	[80, 82–84]
Insulin signaling pathways	Negatively modulates normal IST via IRS-1 and IRS-2, IKK-β activity, Akt, GSK-3, AMPK, and mTOR activity and p38 MAPK-dependent molecular pathways	[91–96, 100–102]
Inflammatory events	Increase inflammatory responses which in turn induces insulin resistance in several pathways	[104, 106–109]
Mitochondrial dysfunction	Impairs normal function of mitochondria thereby reduces cellular capacity for glucose uptake by GLUT-4 transporters	[100, 130–133, 135]

PPAR-γ: peroxisome proliferator-activated receptor gamma; IST: insulin signaling transduction; CEB/Ps: CCAAT enhancer-binding proteins; HIF-1α: hypoxia-inducible factors alpha; MEF2: myocyte enhancer factor 2; IRS-1: insulin receptor substrate-1; Akt: protein kinase B; IKK-β: inhibitor of nuclear factor kappa B; GSK-3: glycogen synthase kinase 3; AMPK: AMP-activated protein kinase; mTOR: mammalian target of rapamycin; p38 MAPK: p38 mitogen-activated protein kinases.