In a type 2 diabetic nephropathy rat model, the improvement of obesity by a low calorie diet reduces oxidative/carbonyl stress and prevents diabetic nephropathy

Nangaku, Masaomi; Izuhara, Yuko; Usuda, Nobuteru; Inagi, Reiko; Shibata, Takeo; Sugiyama, Satoshi; Kurokawa, Kiyoshi; Strihou, Charles van Ypersele de; Miyata, Toshio

doi:10.1093/ndt/gfi096

Cited by 66 publications

(51 citation statements)

References 35 publications

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“…This strain manifested a clustering of abdominal obesity, hypertension, hyperinsulinemia, hypertriglyceridemia, and elevated free fatty acids at 17 wk of age, fulfilling the criteria of metabolic syndrome. Podocyte injury was reported previously in this animal model, but the analysis was made at a later stage, when other abnormalities such as tubulointerstitial changes are evident (10,29). Our findings indicate that podocyte injury should be an early key manifestation in the nephropathy of this model, because at this phase, we did not detect apparent renal morphologic changes or tubulointerstitial inflammatory alterations.…”

Section: Discussionsupporting

confidence: 62%

Enhanced Aldosterone Signaling in the Early Nephropathy of Rats with Metabolic Syndrome

Nagase¹,

Yoshida²,

Shibata³

et al. 2006

Journal of the American Society of Nephrology

232

209

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Metabolic syndrome is an important risk factor for proteinuria and chronic kidney disease independent of diabetes and hypertension; however, the underlying mechanisms have not been elucidated. Aldosterone is implicated in target organ injury of obesity-related disorders. This study investigated the role of aldosterone in the early nephropathy of 17-wk-old SHR/ NDmcr-cp, a rat model of metabolic syndrome. Proteinuria was prominent in SHR/NDmcr-cp compared with nonobese SHR, which was accompanied by podocyte injury as evidenced by foot process effacement, induction of desmin and attenuation of nephrin. Serum aldosterone level, renal and glomerular expressions of aldosterone effector kinase Sgk1, and oxidative stress markers all were elevated in SHR/NDmcr-cp. Mineralocorticoid receptors were expressed in glomerular podocytes. Eplerenone, a selective aldosterone blocker, effectively improved podocyte damage, proteinuria, Sgk1, and oxidant stress. An antioxidant tempol also alleviated podocyte impairment and proteinuria, along with inhibition of Sgk1. As for the mechanisms of aldosterone excess, visceral adipocytes that were isolated from SHR/NDmcr-cp secreted substances that stimulate aldosterone production in adrenocortical cells. The aldosterone-releasing activity of adipocytes was not inhibited by candesartan. Adipocytes from nonobese SHR did not show such activity. In conclusion, SHR/NDmcr-cp exhibit enhanced aldosterone signaling, podocyte injury, and proteinuria, which are ameliorated by eplerenone or tempol. The data also suggest that adipocyte-derived factors other than angiotensin II might contribute to the aldosterone excess of this model.

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Section: Discussionsupporting

confidence: 62%

Enhanced Aldosterone Signaling in the Early Nephropathy of Rats with Metabolic Syndrome

Nagase¹,

Yoshida²,

Shibata³

et al. 2006

Journal of the American Society of Nephrology

232

209

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“…Morphometric analysis of image was done by the computer software (Cell*, Olympus Soft Imaging Solution GmbH). The morphologic changes in glomeruli, arterioles and tubular epithelium were semi quantitatively evaluated according to previous studies [23,24]. …”

Section: Histopathological Examination Of Kidney Tissuesmentioning

confidence: 99%

Aqueous and Methanolic Extracts of Palm Date Seeds and Fruits (Phoenix dactylifera) Protects against Diabetic Nephropathy in Type II Diabetic Rats

Mousalamy¹,

Al-Shatri²

2016

Biochemistry & Physiology: Open Access

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Objective: The present study examined the effects of aqueous and methanolic extracts of palm dates (fruits and seeds) on diabetic nephropathy in a rat model of type 2 DM.Methods: Sixty male albino rats subdivided into a) normal control (NC) group, b) diabetic control (DM) group, c) aqueous fruit extract (AFE) group, d) methanolic fruit extract (MFE) group, e) aqueous seed extract (ASE) group and f) methanolic seed extract (ASE) group. Treatment with both extracts done for 15 weeks after induction of type 2 DM. by the end of experiment fasting blood glucose, serum lipid profile, creatinine, urea, uric acid, urinary albumin excretion, kidney tissue MDA, catalase, SOD, GSH were measured and kidney histopathological examination was done.Results: Diabetic untreated rats showed significant hyperglycemia and hyperlipidemia and deterioration in kidney functions and morphology with enhanced oxidative stress in kidney tissues. On other hand, rats treated with either aqueous or methanolic fruit or seed extracts showed significant improvement in all studied parameters compared to DM group (p<0.05). However, the effects of fruit extracts especially aqueous extract were more powerful than seed extracts. Conclusion:Aqueous and methanolic fruit and seed extracts of palm date protect kidneys from diabetic nephropathy in rats which might be due to their antioxidant properties.Citation: El-Mousalamy AMD, Hussein AAM, Mahmoud SA, Abdelaziz A, Shaker G (2016) Aqueous and Methanolic Extracts of Palm Date Seeds and Fruits (Phoenix dactylifera) Protects against Diabetic Nephropathy in Type II Diabetic Rats. Biochem Physiol 5: 205.

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“…22,23 As examples, SIRT1 regulates glucose or lipid metabolism, BP, and oxidative stress, which are all closely associated with kidney disease. [24][25][26][27][28] In addition, SIRT1 protects the proximal tubular, [29][30][31] medullary, 32 and mesangial cells. 33,34 Several studies have also suggested the possibility of a protective effect of SIRT1 on podocytes [35][36][37] ; however, the molecular mechanism of the function of SIRT1 expressed in podocytes remains unclear.…”

mentioning

confidence: 99%

Sirtuin1 Maintains Actin Cytoskeleton by Deacetylation of Cortactin in Injured Podocytes

Motonishi¹,

Nangaku²,

Wada³

et al. 2015

Journal of the American Society of Nephrology

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Recent studies have highlighted the renoprotective effect of sirtuin1 (SIRT1), a deacetylase that contributes to cellular regulation. However, the pathophysiologic role of SIRT1 in podocytes remains unclear. Here, we investigated the function of SIRT1 in podocytes. We first established podocyte-specific Sirt1 knockout (SIRT1 pod2/2 ) mice. We then induced glomerular disease by nephrotoxic serum injection. The increase in urinary albumin excretion and BUN and the severity of glomerular injury were all significantly greater in SIRT1 pod2/2 mice than in wild-type mice. Western blot analysis and immunofluorescence showed a significant decrease in podocyte-specific proteins in SIRT1 pod2/2 mice, and electron microscopy showed marked exacerbation of podocyte injury, including actin cytoskeleton derangement in SIRT1 pod2/2 mice compared with wild-type mice. Protamine sulfate-induced podocyte injury was also exacerbated by podocyte-specific SIRT1 deficiency. In vitro, actin cytoskeleton derangement in H 2 O 2 -treated podocytes became prominent when the cells were pretreated with SIRT1 inhibitors. Conversely, this H 2 O 2 -induced derangement was ameliorated by SIRT1 activation. Furthermore, SIRT1 activation deacetylated the actin-binding and -polymerizing protein cortactin in the nucleus and facilitated deacetylated cortactin localization in the cytoplasm. Cortactin knockdown or inhibition of the nuclear export of cortactin induced actin cytoskeleton derangement and dissociation of cortactin from F-actin, suggesting the necessity of cytoplasmic cortactin for maintenance of the actin cytoskeleton. Taken together, these findings indicate that SIRT1 protects podocytes and prevents glomerular injury by deacetylating cortactin and thereby, maintaining actin cytoskeleton integrity.

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In a type 2 diabetic nephropathy rat model, the improvement of obesity by a low calorie diet reduces oxidative/carbonyl stress and prevents diabetic nephropathy

Abstract: The present findings suggest a direct role of obesity in the generation of a localized oxidative stress and AGE formation, directly responsible for DN.

Cited by 66 publications

References 35 publications

Enhanced Aldosterone Signaling in the Early Nephropathy of Rats with Metabolic Syndrome

Enhanced Aldosterone Signaling in the Early Nephropathy of Rats with Metabolic Syndrome

Aqueous and Methanolic Extracts of Palm Date Seeds and Fruits (Phoenix dactylifera) Protects against Diabetic Nephropathy in Type II Diabetic Rats

Sirtuin1 Maintains Actin Cytoskeleton by Deacetylation of Cortactin in Injured Podocytes

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