Dataset Information

Nitric oxide metabolism is impaired by type 1 diabetes and diabetic nephropathy.

ABSTRACT: Diabetes leads to reduced nitric oxide bioavailability, resulting in endothelial dysfunction. However, overproduction of nitric oxide due to hyperglycaemia is associated with oxidative stress and tissue damage. The objective of this study was to characterise nitric oxide production (NO) and added nitrite and nitrate (NO2 -+NO3 -) concentration in the blood and urine of patients with and without diabetic nephropathy. A total of 268 patients with type 1 diabetes and 69 healthy subjects were included. Diabetic nephropathy was defined as macroalbuminuria and/or estimated glomerular filtration rate below 60 ml/min/1.73 cm2. NO2 -+NO3 - concentration was measured by Griess reaction. Production of NO was detected by electron paramagnetic resonance spectroscopy. Blood NO was demonstrated to be higher (P<0.001) and serum NO2 -+NO3 - was lower (P=0.003) in patients with type 1 diabetes and no nephropathy vs. healthy subjects. However, serum NO2 -+NO3 - concentration in patients with diabetes and nephropathy did not differ from the levels observed in healthy controls. Urine excretion of NO2 -+NO3 - was significantly decreased in patients with nephropathy, compared with patients without diabetic kidney disease (P=0.006) and healthy subjects (P=0.010). A significant positive correlation was observed between urine NO2 -+NO3 - and estimated glomerular filtration rate in patients with type 1 diabetes (P=0.002) and healthy subjects (P=0.008). Estimated glomerular filtration rate, albuminuria and diabetic nephropathy status were significant predictors of the whole blood NO and NO2 -+NO3 - in serum and urine in patients with type 1 diabetes, as identified by linear regression models. The present study concludes that NO metabolism is impaired by type 1 diabetes and diabetic nephropathy.

SUBMITTER: Sokolovska J

PROVIDER: S-EPMC7100134 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Nitric oxide metabolism is impaired by type 1 diabetes and diabetic nephropathy.

Sokolovska Jelizaveta J Dekante Alise A Baumane Larisa L Pahirko Leonora L Valeinis Janis J Dislere Kristine K Rovite Vita V Pirags Valdis V Sjakste Nikolajs N

Biomedical reports 20200304 5

Diabetes leads to reduced nitric oxide bioavailability, resulting in endothelial dysfunction. However, overproduction of nitric oxide due to hyperglycaemia is associated with oxidative stress and tissue damage. The objective of this study was to characterise nitric oxide production (NO) and added nitrite and nitrate (NO2 -+NO3 -) concentration in the blood and urine of patients with and without diabetic nephropathy. A total of 268 patients with type 1 ...[more]

PMID: 32257188

Similar Datasets

Project description:Aims/introductionThe role of the renal nitric oxide (NO) system in the pathophysiology of diabetic nephropathy constitutes a very challenging and fertile field for future investigation. The purpose of the present study was to investigate whether NO donors can attenuate diabetic renal fibrosis and apoptosis through modulating oxidative-and nitrosative-stress, and Wnt signaling using in vivo diabetic models.Materials and methodsDiabetic rat was induced by a single intraperitoneal injection of streptozotocin. Rats in each group were intraperitoneally given 2,2'-(hydroxynitrosohydrazino)bis-ethanamine (1 U/kg/day) and vehicle for 28 and 56 consecutive days. Expression of the oxidative-and nitrosative-stress, and Wnt signaling components were examined in kidneys from diabetic animals by quantitative reverse transcription polymerase chain reaction, western blot analysis and immunohistochemical staining.ResultsNO donor treatment significantly reduced the ratio of kidney weight to bodyweight and proteinuria. This treatment also significantly restored the suppressive effect of diabetes on urinary NO2 + NO3 levels. Immunohistochemistry showed that NO donor treatment significantly reduced transforming growth factor (TGF)-?1, fibronectin, cleaved caspase-3 and triphosphate-biotin nick end-labeling expression in the glomeruli of diabetic rats. We found that diabetes promoted 8-hydroxy-2'-deoxyguanosine, and peroxynitrite expression coincided with reduced endothelial NO synthase expression in glomeruli. Interestingly, NO donor treatment completely removed oxidative stress and nitrosative stress, and restored endothelial NO synthase expression in diabetic renal glomeruli. Immunohistomorphometry results showed that NO donor treatment significantly restored suppressed Wnt5a expression and ?-catenin immunoreactivities in glomeruli. Based on laser-captured microdissection for quantitative reverse transcription polymerase chain reaction, diabetes significantly increased TGF-?1, and fibronectin expression coincided with depressed Wnt5a expression. NO donor treatment reduced TGF-?1, fibronectin activation, and the suppressing effect of diabetes on Wnt5a and ?-catenin expression in renal glomeruli.ConclusionsNO donor treatment alleviates extracellular matrix accumulation and apoptosis in diabetic nephropathy in vivo by not only preventing the diabetes-mediated oxidative and nitrostative stress, but also restoring downregulation of endothelial NO synthase expression and Wnt/?-catenin signaling. These findings suggest that modulation of NO is a viable alternative strategy for rescuing diabetic renal injury.

Project description:BackgroundNitric oxide (NO) has numerous functions in the kidney, including control of renal and glomerular hemodynamics, by interfering at multiple pathological and physiologically critical steps of nephron function. Endothelial NOS (eNOS) gene has been considered a potential candidate gene to diabetic nephropathy (DN) susceptibility. Endothelial nitric oxide synthase gene (eNOS-3) polymorphisms have been associated with DN, however some studies do not confirm this association. The analyzed polymorphisms were 4b/4a, T-786C, and G986T.MethodsThe Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was used in this report. Case-control studies that had diabetic patients with DN as cases and diabetic patients without nephropathy as controls, as well as that evaluated at least one of the three polymorphisms of interest were considered eligible. All studies published up until December 31st, 2012 were identified by searching electronic databases. Hardy-Weinberg equilibrium assessment was performed. Gene-disease association was measured using odds ratio estimation based on the following genetic contrast/models: (1) allele contrast; (2) additive model; (3) recessive model; (4) dominant model and (4) co-dominant model.ResultsTwenty-two studies were eligible for meta-analysis (4b/a: 15 studies, T-786C: 5 studies, and G984T: 12 studies). Considering 4b/a polymorphism, an association with DN was observed for all genetic models: allele contrast (OR = 1.14, CI: 1.04-1.25); additive (OR = 1.77, CI: 1.37-2.28); recessive (OR = 1.77, CI: 1.38-2,27); dominant (OR = 1.12, CI: 1.01-1.24), with the exception for co-dominance model. As well, T-786C polymorphism showed association with all models, with exception for co-dominance model: allele contrast (OR = 1.22, CI: 1.07-1.39), additive (OR = 1.52, CI: 1.18-1.97), recessive (OR = 1.50, CI: 1.16-1.93), and dominant (OR = 1.11, CI: 1.01-1.23). For the G894T polymorphism, an association with DN was observed in allelic contrast (OR = 1.12, CI: 1.03-1.25) and co-dominance models (OR = 1.13, CI: 1.04-1.37).ConclusionsIn the present study, there was association of DN with eNOS 4b/a and T-786C polymorphism, which held in all genetic models tested, except for co-dominance model. G894T polymorphism was associated with DN only in allele contrast and in co-dominance model. This data suggested that the eNOS gene could play a role in the development of DN.

Dataset Information

Nitric oxide metabolism is impaired by type 1 diabetes and diabetic nephropathy.

Publications

Nitric oxide metabolism is impaired by type 1 diabetes and diabetic nephropathy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets