Table of Contents Author Guidelines Submit a Manuscript
Journal of Diabetes Research
Volume 2013, Article ID 254529, 8 pages
Research Article

Outcome of Acute Renal Injury in Diabetic Mice with Experimental Endotoxemia: Role of Hypoxia-Inducible Factor-1α

1Laboratory of Renal Physiology and Experimental Nephrology, Department of Biological Systems/Physiology Unit, University of Alcalá, Alcalá de Henares, Madrid, Spain
2Department of Biological Systems/Physiology Unit, University of Alcalá, Alcalá de Henares, Madrid, Spain
3Department of Clinical Chemistry University Hospital “Príncipe de Asturias”, University of Alcalá, Alcalá de Henares, Spain
4Cell Response to Ischemia Laboratory, Department of Systems Disorders and Cancer, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, Spain

Received 15 January 2013; Accepted 5 July 2013

Academic Editor: Shahidul Islam

Copyright © 2013 A. Ortega 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.


The role of diabetic nephropathy in the outcome of acute renal injury (AKI) is not well defined. Herein we evaluate the outcome of lipopolysaccharide- (LPS-) induced AKI in streptozotocin-induced diabetes, as well as the potential role of Hypoxia Inducible Factor (HIF-1α) in this condition. Although 6 h after LPS injection all mice developed a decrease in renal function, proteinuric diabetic mice showed a better recovery of this parameter throughout the study (72 h). Both HIF-1α and vascular endothelium growth factor (VEGF) were found to be upregulated in diabetic mice. After LPS injection, all animals showed an upregulation of these factors, although it was higher in the diabetic group. Glycated albumin (GA) was found to upregulate HIF-1α in HK-2 cells, which resulted in increased production of VEGF. Interestingly, LPS cooperated with GA to induce HIF-1α upregulation. In conclusion, diabetic mice display a better recovery of AKI after experimental endotoxemia. Moreover, these animals showed an increased expression of both HIF-1α and VEGF that was reproduced by incubating renal cells with GA. Since VEGF is considered a survival factor for tubular cells, our findings suggest that diabetes displays HIF-1α upregulation that might function as a “precondition state” offering protection from endotoxic AKI.