Sp445increased Oxidative Stress in Diabetic Nephropathy and Relationship to Soluble Klotho Levels

İnci, Ayça; Sarı, Funda; Sarıkaya, Metin; Yılmaz, Üstün; Çoban, Melahat; Gul, Semih; Akın, Olgun; Şahintürk, Yasin; Yılmaz, Necat

doi:10.1093/ndt/gfx149.sp445

Cited by 15 publications

(15 citation statements)

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“…These results suggest that decreased mtDNA-CN in the peripheral blood of DN patients may be a consequence of diabetes-induced oxidative stress. In support of this notion, previous studies have indicated that diabetic patients with DN have higher oxidative stress than non-diabetic individuals (36,37). Furthermore, a study by Zhou et al (38) reported that reduced peripheral blood mtDNA-CN as a result of hyperglycemia-induced oxidative stress is closely associated with glucose-stimulated insulin secretion in diabetic patients.…”

Section: Discussionmentioning

confidence: 83%

Peripheral blood mitochondrial DNA copy number as a novel potential biomarker for diabetic nephropathy in type�2 diabetes patients

et al. 2018

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The mitochondrial DNA copy number (mtDNA-CN) is a surrogate measure of mitochondrial function and altered mtDNA-CN reflects the oxidant-induced cell damage. A previous study by our group demonstrated that a reduction in the renal mtDNA-CN is implicated in the pathogenesis of diabetic nephropathy (DN), a leading cause of end-stage renal disease in diabetic patients. In the present study, it was investigated whether the mtDNA-CN in the peripheral blood may be utilized as a biomarker for DN in type 2 diabetes (T2D) patients. The study included 50 non-diabetic and 100 diabetic subjects. The diabetic subjects were sub-divided based on their albumin-to-creatinine ratio (ACR) into T2D patients with normoalbuminuria (n=50), DN patients with microalbuminuria (n=29) and DN patients with macroalbuminuria (n=21). The mtDNA-CN was measured in the peripheral blood by real-time polymerase chain reaction analysis. Patients with DN had a lower mtDNA-CN than patients with T2D and healthy controls (P<0.05). A sub-group analysis with stratification by the ACR indicated that a decreased mtDNA-CN was associated with the severity and the presence of DN, as it was lower in DN patients with macroalbuminuria than in DN patients with microalbuminuria and T2D patients with normoalbuminuria (P<0.01). The area under the receiver operating characteristic curve (AUC) for mtDNA-CN was 0.916 (sensitivity, 86% and specificity, 74%) and 0.961 (sensitivity, 96% and specificity, 88%) for differentiating DN patients from T2D patients without DN and from healthy controls, respectively. Furthermore, the AUC of mtDNA-CN for differentiating DN patients with microalbuminuria from those with macroalbuminuria was 0.895 (sensitivity, 83% and specificity, 85%). Multivariate analysis revealed that the mtDNA-CN was significantly associated with the occurrence and progression of DN, even after adjustment for age, mean blood pressure, glycated haemoglobin A1c and total cholesterol (P<0.05). In patients with DN, a decreased mtDNA-CN was negatively correlated with albuminuria and conventional risk factors for DN, and was positively correlated with the estimated glomerular filtration rate. The present results therefore suggest the utilization of circulating mtDNA-CN as a novel biomarker for the early diagnosis of DN and indicate the significance of decreased mtDNA-CN as another independent risk factor for DN.

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Section: Discussionmentioning

confidence: 83%

Peripheral blood mitochondrial DNA copy number as a novel potential biomarker for diabetic nephropathy in type�2 diabetes patients

et al. 2018

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“…In addition, many studies have shown that klotho can be considered as a significant humoral factor associated with type 2 diabetes (10). Analyses of glucose and insulin tolerance showed that klotho may have inhibitory effect on insulin activity, however, its interference molecular mechanisms have not elucidated, yet (2).…”

Section: Introductionmentioning

confidence: 99%

Klotho induces insulin resistance possibly through interference with GLUT4 translocation and activation of Akt, GSK3β, and PFKfβ3 in 3T3-L1 adipocyte cells

et al. 2019

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Klotho is considered as an anti-aging factor inducing insulin resistance and involved in type 2 diabetes. However, mechanisms by which klotho induces insulin resistance remain to be understood. Thus, in this study, we aimed to evaluate possible interference points of klotho with insulin signaling pathways in 3T3-L1 adipocyte cells by focusing on phosphorylation levels of Akt, GSK3β, PFK-fβ3, and GLUT4 translocation. Differentiation of 3T3-L1 cells to the adipocyte-like cells were performed using specific differentiation kit and confirmed by mRNA expression assay of PPARγ using qRT-PCR, and Sudan black staining of lipid droplets. Then cells were co-treated with klotho and insulin. Expression and translocation of GLUT4 mRNA were evaluated using qRT-PCR and Alexa flour 488 conjugated GLUT4 antibody, respectively. P-Akt/Akt, p-GSK3β/GSK3β, and p-PFKfβ3/PFKfβ3 ratios were determined in insulin and klotho/insulin treated cells using western blot. Our result indicated that GLUT4 expression were decreased to 0.72 ± 0.16 fold in insulin treated cells, however it was calculated 1.12 ± 0.25 fold in klotho/insulin treated cells. In addition, klotho prevented GLUT4 membrane translocation by 27.2% in comparison with insulin-treated cells ( P < 0.05). Interestingly, in insulin/klotho co-treated cells, phospho-levels of Akt, GSK3β, and PFKfβ3 proteins was decreased to 2.34 ± 0.14, 2.29 ± 0.63, and 1.95 ± 0.37 fold in comparison with the insulin cells, ( P < 0.05). In conclusion, our study indicated that klotho induces insulin resistance in adipocytes possibly through prevention of GLUT4 translocation, and interfere with phosphorylation of Akt, GSK3β, and PFKf3β intracellular signaling mediators by insulin.

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“…Liu, et al acquired [27] 31 P magnetic resonance spectroscopy ( 31 P-MRS) to quantify changes in phosphate metabolites and muscle oxygenation in Goto-Kakizaki (GK) non-obese type 2 diabetes (T2D) rats and Wistar (control) rats. Inci, et al did not associated the soluble Klotho (s-Klotho) levels [28] with phosphorus and PTH levels in diabetic nephropathy patients. Brown, et al related [29] the progression of established chronic kidney disease CKD with dietary phosphorus intake, in cats.…”

Section: Discussionmentioning

confidence: 98%

The alterations effects in phosphorus of erythropoietin and U-74389G

Τsompos¹,

Panoulis²,

Triantafyllou³

et al. 2020

Int J Bone Marrow Res

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Aim: This study calculated the eff ects on serum phosphorus (P) levels, after treatment with either of 2 drugs: the erythropoietin (Epo) and the antioxidant lazaroid (L) drug U-74389G. The calculation was based on the results of 2 preliminary studies, each one of which estimated the certain infl uence, after the respective drug usage in an induced ischemia reperfusion (IR) animal experiment. Materials and methods:The 2 main experimental endpoints at which the serum P levels were evaluated was the 60 th reperfusion min (for the groups A, C and E) and the 120 th reperfusion min (for the groups B, D and F). Specially, the groups A and B were processed without drugs, the groups C and D after Epo administration; whereas the groups E and F after the L administration. Results:The fi rst preliminary study of Epo presented a non signifi cant hyperphosphoremic eff ect by 2.46% + 2.02% (pvalue = 0.2168). However, the second preliminary study of U-74389G presented a non signifi cant hypophosphoremic eff ect by 1.09% + 2.01% (pvalue = 0.5771). These 2 studies were co-evaluated since they came from the same experimental setting. The outcome of the co-evaluation was that L is at least 0.4455128-fold [0.4445589 -0.4464687] more hypophosphoremic than Epo (pvalue = 0.0000). Conclusion:The anti-oxidant capacities of U-74389G ascribe at least 0.4455128-fold [0.4445589 -0.4464687] more eff ects than Epo (pvalue = 0.0000).The alterations effects in phosphorus of erythropoietin and U-74389G https://www.heighpubs.org/hbmr https://doi.

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Sp445increased Oxidative Stress in Diabetic Nephropathy and Relationship to Soluble Klotho Levels

Cited by 15 publications

References 0 publications

Peripheral blood mitochondrial DNA copy number as a novel potential biomarker for diabetic nephropathy in type�2 diabetes patients

Peripheral blood mitochondrial DNA copy number as a novel potential biomarker for diabetic nephropathy in type�2 diabetes patients

Klotho induces insulin resistance possibly through interference with GLUT4 translocation and activation of Akt, GSK3β, and PFKfβ3 in 3T3-L1 adipocyte cells

The alterations effects in phosphorus of erythropoietin and U-74389G

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