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

Abstract

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.

The impact of acute kidney injury in diabetes mellitus

“…This therefore suggests that a better renal outcome is a consistent finding related to diabetes, rather than a difference in the nature of AKI itself. These observations are consistent with experimental studies suggesting that the diabetic state may limit acute renal injury through ‘pre‐conditioining’ and also facilitate recovery by priming regenerative mechanisms …”

Mir‐217 promotes inflammation and fibrosis in high glucose cultured rat glomerular mesangial cells via Sirt1/HIF‐1α signaling pathway

“…As previously viewed, hypoxia already existed in the subclinical stage of DN, and expression of HIF‐1α also increased . Ortega et al have shown that in addition to hypoxia, some factors, such as inflammation and stress, also up‐regulate the expression of HIF‐1α.…”

The impact of diabetes on outcomes, length of stay and costs in acute kidney injury patients: a cross-sectional multicenter study in China

“…However, we observed that diabetes was not independently associated with mortality in whole AKI patients after adjusted for age, gender, and regions. The possible explanations for this phenomenon are diabetic state postponed renal injury through 'pre-conditioning' [25] and priming regeneration mechanisms [23].…”