Table of Contents Author Guidelines Submit a Manuscript
Journal of Diabetes Research
Volume 2017, Article ID 8379327, 30 pages
Review Article

Diabetes-Induced Reactive Oxygen Species: Mechanism of Their Generation and Role in Renal Injury

Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe (ULM), Pharmacy Building, 1800 Bienville Dr., Monroe, LA 71201, USA

Correspondence should be addressed to Keith E. Jackson; ude.mlu@noskcajk

Received 12 September 2016; Accepted 7 December 2016; Published 9 January 2017

Academic Editor: Carlos Martinez Salgado

Copyright © 2017 Selim Fakhruddin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Diabetes induces the onset and progression of renal injury through causing hemodynamic dysregulation along with abnormal morphological and functional nephron changes. The most important event that precedes renal injury is an increase in permeability of plasma proteins such as albumin through a damaged glomerular filtration barrier resulting in excessive urinary albumin excretion (UAE). Moreover, once enhanced UAE begins, it may advance renal injury from progression of abnormal renal hemodynamics, increased glomerular basement membrane (GBM) thickness, mesangial expansion, extracellular matrix accumulation, and glomerulosclerosis to eventual end-stage renal damage. Interestingly, all these pathological changes are predominantly driven by diabetes-induced reactive oxygen species (ROS) and abnormal downstream signaling molecules. In diabetic kidney, NADPH oxidase (enzymatic) and mitochondrial electron transport chain (nonenzymatic) are the prominent sources of ROS, which are believed to cause the onset of albuminuria followed by progression to renal damage through podocyte depletion. Chronic hyperglycemia and consequent ROS production can trigger abnormal signaling pathways involving diverse signaling mediators such as transcription factors, inflammatory cytokines, chemokines, and vasoactive substances. Persistently, increased expression and activation of these signaling molecules contribute to the irreversible functional and structural changes in the kidney resulting in critically decreased glomerular filtration rate leading to eventual renal failure.