Korean Diabetes J.  2008 Oct;32(5):389-398. 10.4093/kdj.2008.32.5.389.

Oxidative Stress and Cell Dysfunction in Diabetes: Role of ROS Produced by Mitochondria and NAD(P)H Oxidase

• Kim SS
• Son SM

• KMID: 2298076
• DOI: http://doi.org/10.4093/kdj.2008.32.5.389

Abstract

Oxidative stress has been considered to be a major contributor to the pathogenesis of the diabetic macrovascular and microvascular complications. In the absence of an appropriate antioxidant defense mechanism, increased oxidative stress leads to the activation of stress-sensitive intracellular signaling pathways and the formation of gene products that cause damage and contribute to the late complications ofdiabetes. The source of reactive oxygen species (ROS) in the pancreatic beta cells and insulin sensitive cells has postulated to be the mitochondrial electron transport chain. NAD(P)H oxidase-dependent ROS production is also important as the source both in pancreatic beta cells and other cells. NAD(P)H oxidase mediated ROS can alter parameters of signal transduction, insulin secretion, insulin action, cell proliferation and cell death. Additionally, oxidative stress as the pathogenic mechanism linking insulin resistance with dysfunction of both pancreatic beta cells and endothelial cells, eventually leads to diabetes and its complications. Further investigation of the mechanisms and its therapeutic interventions based on focusing NAD(P)H oxidase associated ROS production in the islet cells and other islet cells are needed

Keyword

Diabetes; Mitochondria; NAD(P)H oxidiase; Oxidative stress; ROS

MeSH Terms

Cell Death
Cell Proliferation
Electron Transport
Endothelial Cells
Insulin
Insulin Resistance
Insulin-Secreting Cells
Islets of Langerhans
Mitochondria
NADPH Oxidase
Oxidative Stress
Reactive Oxygen Species
Signal Transduction
Insulin
NADPH Oxidase
Reactive Oxygen Species

Figure

• 

  Fig. 1 Overview of the sources of ROS in diabetes and their links to atherosclerosis. oxLDL, oxidized LDL; FFA, free fatty acid; AGEs, advanced glycation end-products; VSMC, vascular smooth muscle cells; ROS, reactive oxygen species.

• 

  Fig. 2 Production of reactive oxygen species (ROS) in a generic cell type (Adapted from Anteriosclero Thromb Vasc Biol 24:816-23, 2004 & J Physiol 583:9-24, 2007).

• 

  Fig. 3 Overview of PKC-dependent activation and induction of eNOS and vascular NAD(P)H oxidase. IRS-1, insulin receptor substrate-1; eNOS, endothelial nitric oxide synthase (Adapted from Arterioscler Thromb Vasc Biol 25:487-96, 2005).

• 

  Fig. 4 Induction of insulin resistance by oxidative stress. FFA, free fatty acid; ROS, Reactive oxygen species; RNS, Reactive nitogen species; IRS-1, insulin receptor substrate-1; iNOS, inducible nitric oxide synthase; NO, nitric oxide (Adapted from J Physiol 583:9-24, 2007).

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