Type 2 diabetes mellitus in mice aggravates the renal impact of hemorrhagic shock.
The objectives of this study were to determine whether type 2 diabetic mice would exhibit a more severe renal impact of hemorrhagic shock (HS) based on a recently described model of acute kidney injury and to determine the impact of HS on renal responses to hypoxia. We induced HS or sham procedure in type 2 diabetic and obese db/db mice. Creatininemia, glomerular filtration rate, urine output, histologic injury score, and kidney inductible molecule 1 mRNA were used to investigate the renal impact of HS. Tissular hypoxia and its impact were quantified using pimonidazole immunostaining and mRNA of hypoxic inducible factor, vascular endothelial growth factor receptors 1 and 2, Tie-2, endothelial nitric oxide synthase, and inducible nitric oxide synthase. Diabetic mice exhibiting mild diabetic nephropathy express hypoxic signals at baseline. The renal impact of HS was more severe in diabetic mice, with a worsening of tissular hypoxia and an altered response to hypoxia. Furthermore, endothelial nitric oxide synthase was highly overexpressed in diabetic shocked mice when compared with nondiabetic shocked mice. Renal impact of HS in type 2 diabetic mice is more intense than in nondiabetic ones. Preexisting hypoxia during diabetes could result in a renal preconditioning that modifies endothelial and tissular responses to acute kidney injury.
Département d'anesthésie réanimation, Université Paul Sabatier Toulouse III, CHU Rangueil, France.
Virginie
V
Dupuy
Nicolas
N
Mayeur
Marie
M
Buléon
Acil
A
Jaafar
Talal
T
Al Saati
Stéphane
S
Schaak
Françoise
F
Praddaude
Vincent
V
Minville
Ivan
I
Tack
D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005786:Gene Expression Regulation; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D012771:Shock, Hemorrhagic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology