Chronically increased intrarenal angiotensin II causes nephropathy in an animal model of type 2 diabetes

Sharma, Ram; Sharma, Mukut; Reddy, S. Raghupathi Rami; Savin, Virginia J.; Nagaria, Abdul Mateen; Wiegmann, Thomas

doi:10.2741/1853

Cited by 38 publications

(40 citation statements)

References 40 publications

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“…This action of ANG II is way to be mediated chiefly with transforming growth factor-beta, which stimulates the synthesis and decreases the degradation of extracellular matrix components, as well as collagen types and fibronectin. 31 In our study, in diabetic rats (without treatment), volume of glomerular area, glomerulosclerosis, fibronectin and i-NOS expression were increased significantly when compared to control group (Group 1). However, a statistically meaningful reduction was determined in glomerulus area in diabetic rat group receiving enalapril and TMZ when compared to control rat group in our study.…”

Section: Discussionsupporting

confidence: 47%

Experimental comparison of protective characteristics of enalapril and trimetazidine in diabetic nephropathy

Karadeniz

Çavuşoğlu

Türkmen³

et al. 2014

Renal Failure

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Section: Discussionsupporting

confidence: 47%

Experimental comparison of protective characteristics of enalapril and trimetazidine in diabetic nephropathy

Karadeniz

Çavuşoğlu

Türkmen³

et al. 2014

Renal Failure

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“…The increases in ROS formation and urine isoprostanes in the ZO rat, independent of elevations in SBP, further suggest an association between insulin resistance/hyperinsulinemia, oxidative stress, and filtration barrier injury. There is accumulating data supporting the notion that the podocyte is susceptible to immunologic and inflammatory injury from ROS generated by endothelial cells [3, 4,35,36,37]. One proposed mechanism is that insulin resistance and the compensatory hyperinsulinemia may lead to enhanced oxidative stress and inflammation in the glomerulus with resultant downregulation of nephrin, an important protein necessary for maintenance of the slit pore diaphragm of the podocyte [35,36,37].…”

Section: Discussionmentioning

confidence: 99%

Insulin Resistance, Oxidative Stress, and Podocyte Injury: Role of Rosuvastatin Modulation of Filtration Barrier Injury

Whaley‐Connell¹,

DeMarco²,

Lastra³

et al. 2007

Am J Nephrol

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Background/Aim: There is an emerging relationship between insulin resistance/hyperinsulinemia, oxidative stress, and glomerular injury manifesting as albuminuria. HMG-CoA reductase inhibitors (statins) have been shown to reduce oxidative stress in the vasculature as well as albuminuria in animal models and in human studies. The glomerular filtration barrier is emerging as a critical determinant of albumin filtration. We investigated the effects of insulin resistance and rosuvastatin or placebo on the glomerular filtration barrier. Method: Young Zucker obese and Zucker lean rats (6–7 weeks old) were treated with the HMG-CoA reductase inhibitor rosuvastatin (10 mg/kg/day) or placebo for 21 days. Results: In the Zucker obese rats, homeostasis model assessment-insulin resistance index, oxidative markers (NADPH oxidase activity, reactive oxygen species, and urine isoprostane formation), podocyte foot process effacement, and albuminuria were increased as compared with Zucker lean controls, independent of increases in systolic blood pressure. Albuminuria correlated with podocyte foot process effacement (r² = 0.61) and insulin level (r² = 0.69). Rosuvastatin treatment improved albuminuria, filtration barrier indices, and oxidative stress via copper/zinc superoxide dismutase. Conclusions: These data indicate that hyperinsulinemia together with insulin resistance is associated with podocyte injury and albuminuria independent of the systolic blood pressure. Further, rosuvastatin modulates filtration barrier injury and albuminuria and improves oxidative stress measures via copper/zinc superoxide dismutase.

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“…It is known that diabetic increases in systemic and renal levels of ANG II and TGF-␤1 play critical roles in diabetic renal pathogenesis (3,28). Other studies also demonstrated the increase in UII levels along with ANG II and TGF-␤1 in the subjects with various pathogeneses (3,6,15,36,37).…”

Section: Diabetic Increases In Uii and Gpr14 Expressions Were Accompamentioning

confidence: 95%

Diabetes-induced upregulation of urotensin II and its receptor plays an important role in TGF-β1-mediated renal fibrosis and dysfunction

Tian¹,

Cai²,

Qi³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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L. Diabetes-induced upregulation of urotensin II and its receptor plays an important role in TGF-␤1-mediated renal fibrosis and dysfunction. Am J Physiol Endocrinol Metab 295: E1234 -E1242, 2008. First published September 16, 2008 doi:10.1152/ajpendo.90672.2008.-Urotensin II (UII) was identified as the ligand for a novel G protein-coupled receptor, GPR14. UII was found not only to have a potent vasoconstrictive action but also to have profibrotic effects in the heart. The present study was to define whether UII and GPR14 also play important roles in diabetes-induced renal fibrosis and dysfunction. Diabetic rats were induced using streptozotocin, and the rat proximal tubular epithelial cells (NRK-52E) were used for the in vitro mechanism study. Results showed that expression of UII and GPR14 was significantly upregulated at both mRNA and protein levels in the diabetic kidneys compared with controls. The upregulated expressions of UII and GPR14 in the kidney were accompanied by significant increases in the renal profibrotic factor transforming growth factor (TGF)-␤1 expression, the renal extracellular matrix (fibronectin and collagen IV) accumulation, and the renal dysfunction (increases in urinal N-acetyl-␤-D-glucosaminidase content, 24-h urinary retinol-binding protein excretion rate, and decrease in creatinine clearance rate). Exposure of NRK-52E cells to 10 Ϫ8 mol/l UII for 48 h caused a significant increase of TGF-␤1, but not ANG II, production that was GPR14-and calcium-dependent, since GPR14 small-interfering RNA and calcium channel blocker nimodipine or calcium chelator EDTA all could abolish the induction of TGF-␤1 by UII. Furthermore, exposure of NRK-52E cells to TGF-␤1 or ANG II also increased UII and GPR14 mRNA expressions. These results suggested that diabetes-induced upregulation of UII and GPR14, most likely through autocrine and/or paracrine mechanisms, plays an important role in TGF-␤1-mediated renal fibrosis and dysfunction. diabetic nephropathy; G protein-coupled receptor 14; renal extracellular matrix accumulation; streptozotocin diabetic rats; angiotensin II; transforming growth factor-␤1 DIABETIC NEPHROPATHY (DN) is one of the major microvascular complications and also the leading cause of the end-stage renal disease (ESRD). Therefore, to develop an effective approach to delay or halt the pathogenic progression toward ESRD in patients with overt DN is urgent (8,17,19). To understand the mechanisms responsible for the initiation and development of the diabetes-induced renal pathogenesis will help us to develop the effectively preventive or therapeutic approaches for DN (19). Many factors play roles in the pathogenesis of DN; for instance, both transforming growth factor ␤1 (TGF-␤1) and ANG II are important factors to promote the development of DN (10,17,19,27).Urotensin II (UII), an 11-amino acid vasoactive peptide, was identified as the ligand for a novel G protein-coupled receptor, GPR14 (also named as urotensin receptor) (13). UII was found to be a powerful vasoconstrictor with potency gre...

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Chronically increased intrarenal angiotensin II causes nephropathy in an animal model of type 2 diabetes

Cited by 38 publications

References 40 publications

Experimental comparison of protective characteristics of enalapril and trimetazidine in diabetic nephropathy

Experimental comparison of protective characteristics of enalapril and trimetazidine in diabetic nephropathy

Insulin Resistance, Oxidative Stress, and Podocyte Injury: Role of Rosuvastatin Modulation of Filtration Barrier Injury

Diabetes-induced upregulation of urotensin II and its receptor plays an important role in TGF-β1-mediated renal fibrosis and dysfunction

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