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Endothelial Toxicity of High Glucose and its by-Products in Diabetic Kidney Disease

by Laetitia Dou 1,* and Noémie Jourde-Chiche 1,2,†
Aix Marseille University, INSERM, INRA, C2VN, Faculté de Pharmacie, 27 Bd Jean Moulin, 13005 Marseille, France
Centre de Néphrologie et Transplantation Rénale, AP-HM, Hôpital de la Conception, 147 Bd Baille, 13005 Marseille, France
Author to whom correspondence should be addressed.
For the French Renal Endothelial Society (FRENDS).
Toxins 2019, 11(10), 578;
Received: 30 August 2019 / Revised: 26 September 2019 / Accepted: 3 October 2019 / Published: 5 October 2019
(This article belongs to the Special Issue The Endothelial Effects of Uremic Toxins)
Alterations of renal endothelial cells play a crucial role in the initiation and progression of diabetic kidney disease. High glucose per se, as well as glucose by-products, induce endothelial dysfunction in both large vessels and the microvasculature. Toxic glucose by-products include advanced glycation end products (AGEs), a group of modified proteins and/or lipids that become glycated after exposure to sugars, and glucose metabolites produced via the polyol pathway. These glucose-related endothelio-toxins notably induce an alteration of the glomerular filtration barrier by increasing the permeability of glomerular endothelial cells, altering endothelial glycocalyx, and finally, inducing endothelial cell apoptosis. The glomerular endothelial dysfunction results in albuminuria. In addition, high glucose and by-products impair the endothelial repair capacities by reducing the number and function of endothelial progenitor cells. In this review, we summarize the mechanisms of renal endothelial toxicity of high glucose/glucose by-products, which encompass changes in synthesis of growth factors like TGF-β and VEGF, induction of oxidative stress and inflammation, and reduction of NO bioavailability. We finally present potential therapies to reduce endothelial dysfunction in diabetic kidney disease. View Full-Text
Keywords: AGEs; diabetic kidney disease; endothelial dysfunction; glucose; polyols AGEs; diabetic kidney disease; endothelial dysfunction; glucose; polyols
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MDPI and ACS Style

Dou, L.; Jourde-Chiche, N. Endothelial Toxicity of High Glucose and its by-Products in Diabetic Kidney Disease. Toxins 2019, 11, 578.

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