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

2007 ◽  
Vol 28 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Adam Whaley-Connell ◽  
Vincent G. DeMarco ◽  
Guido Lastra ◽  
Camila Manrique ◽  
Ravi Nistala ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Podocyte Injury ◽  
Filtration Barrier

scholarly journals Podocyte injury: the role of proteinuria, urinary plasminogen, and oxidative stress

2016 ◽  
Vol 311 (6) ◽  
pp. F1308-F1317 ◽  
Author(s):  
Leopoldo Raij ◽  
Runxia Tian ◽  
Jenny S. Wong ◽  
John C. He ◽  
Kirk N. Campbell
Keyword(s):  
Oxidative Stress ◽  
Glomerular Filtration ◽  
Biologically Active ◽  
Current Evidence ◽  
Glomerular Sclerosis ◽  
Glomerular Diseases ◽  
Podocyte Injury ◽  
Filtration Barrier ◽  
Focal Segmental Glomerular Sclerosis

Podocytes are the key target for injury in proteinuric glomerular diseases that result in podocyte loss, progressive focal segmental glomerular sclerosis (FSGS), and renal failure. Current evidence suggests that the initiation of podocyte injury and associated proteinuria can be separated from factors that drive and maintain these pathogenic processes leading to FSGS. In nephrotic urine aberrant glomerular filtration of plasminogen (Plg) is activated to the biologically active serine protease plasmin by urokinase-type plasminogen activator (uPA). In vivo inhibition of uPA mitigates Plg activation and development of FSGS in several proteinuric models of renal disease including 5/6 nephrectomy. Here, we show that Plg is markedly increased in the urine in two murine models of proteinuric kidney disease associated with podocyte injury: Tg26 HIV-associated nephropathy and the Cd2ap −/− model of FSGS. We show that human podocytes express uPA and three Plg receptors: uPAR, tPA, and Plg-RKT. We demonstrate that Plg treatment of podocytes specifically upregulates NADPH oxidase isoforms NOX2/NOX4 and increases production of mitochondrial-dependent superoxide anion (O2−) that promotes endothelin-1 synthesis. Plg via O2− also promotes expression of the B scavenger receptor CD36 and subsequent increased intracellular cholesterol uptake resulting in podocyte apoptosis. Taken together, our findings suggest that following disruption of the glomerular filtration barrier at the onset of proteinuric disease, podocytes are exposed to Plg resulting in further injury mediated by oxidative stress. We suggest that chronic exposure to Plg could serve as a “second hit” in glomerular disease and that Plg is potentially an attractive target for therapeutic intervention.

scholarly journals Caloric Restriction Reverses Hepatic Insulin Resistance and Steatosis in Rats with Low Aerobic Capacity

Endocrinology ◽  
2010 ◽  
Vol 151 (11) ◽  
pp. 5157-5164 ◽  
Author(s):  
Thomas A. Bowman ◽  
Sadeesh K. Ramakrishnan ◽  
Meenakshi Kaw ◽  
Sang Jun Lee ◽  
Payal R. Patel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Caloric Restriction ◽  
Visceral Obesity ◽  
Insulin Clearance ◽  
Hepatic Insulin Resistance ◽  
The Metabolic Syndrome ◽  
Cell Adhesion Molecule 1 ◽  
Muscle Triglyceride

Rats selectively bred for low aerobic running capacity exhibit the metabolic syndrome, including hyperinsulinemia, insulin resistance, visceral obesity, and dyslipidemia. They also exhibit features of nonalcoholic steatohepatitis, including chicken-wire fibrosis, inflammation, and oxidative stress. Hyperinsulinemia in these rats is associated with impaired hepatic insulin clearance. The current studies aimed to determine whether these metabolic abnormalities could be reversed by caloric restriction (CR). CR by 30% over a period of 2–3 months improved insulin clearance in parallel to inducing the protein content and activation of the carcinoembryonic antigen-related cell adhesion molecule 1, a main player in hepatic insulin extraction. It also reduced glucose and insulin intolerance and serum and tissue (liver and muscle) triglyceride levels. Additionally, CR reversed inflammation, oxidative stress, and fibrosis in liver. The data support a significant role of CR in the normalization of insulin and lipid metabolism in liver.

Abstract 357: Hepatic ERK2 Suppresses Endoplasmic Reticulum Stress, Leading to Protection from Oxidative Stress and Endothelial Dysfunction

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Takehiko Kujiraoka ◽  
Yasushi Satoh ◽  
Makoto Ayaori ◽  
Yasunaga Shiraishi ◽  
Yuko Arai-Nakaya ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Endoplasmic Reticulum ◽  
Fatty Acid ◽  
Endothelial Dysfunction ◽  
Er Stress ◽  
Vascular Complications ◽  
Metabolic Remodeling ◽  
And Oxidative Stress

Background Insulin signaling comprises 2 major cascades, the IRS/PI3K/Akt and Ras/Raf/MEK/ERK pathways. Many studies on the tissue-specific effects of the former pathway had been conducted, however, the role of the latter cascade in tissue-specific insulin resistance had not been investigated. High glucose/fatty acid toxicity, inflammation and oxidative stress, all of which are associated with insulin resistance, can activate ERK. Liver plays a central role of metabolism and hepatosteatosis (HST) is associated with vascular diseases. The aim of this study is to elucidate the role of hepatic ERK2 in HST, metabolic remodeling and endothelial dysfunction. Methods Serum biomarkers of vascular complications in human were compared between subjects with and without HST diagnosed by echography for regular medical checkup. Next, we created liver-specific ERK2 knockout mice (LE2KO) and fed them with a high-fat/high-sucrose diet (HFHSD) for 20 weeks. The histological analysis, the expression of hepatic sarco/endoplasmic reticulum (ER) Ca 2+ -ATPase 2 (SERCA2) and glucose-tolerance/insulin-sensitivity (GT/IS) were tested. Vascular superoxide production and endothelial function were evaluated with dihydroethidium staining and isometric tension measurement of aorta. Results The presence of HST significantly increased HOMA-IR, an indicator of insulin resistance or atherosclerotic index in human. HFHSD-fed LE2KO revealed a marked exacerbation in HST and metabolic remodeling represented by the impairment of GT/IS, elevated serum free fatty acid and hyperhomocysteinemia without changes in body weight, blood pressure and serum cholesterol/triglyceride levels. In the HFHSD-fed LE2KO, mRNA and protein expressions of hepatic SERCA2 were significantly decreased, which resulted in hepatic ER stress. Induction of vascular superoxide production and remarkable endothelial dysfunction were also observed in them. Conclusions Hepatic ERK2 revealed the suppression of hepatic ER stress and HST in vivo , which resulted in protection from vascular oxidative stress and endothelial dysfunction. HST with hepatic ER stress can be a prominent risk of vascular complications by metabolic remodeling and oxidative stress in obese-related diseases.

scholarly journals The Protective Effect of Shen Qi Wan on Adenine-Induced Podocyte Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yiyou Lin ◽  
Jieying Zhang ◽  
Yunbo Fu ◽  
Liting Ji ◽  
Luning Lin ◽  
...  
Keyword(s):  
Metabolic Disorders ◽  
Kidney Injury ◽  
Glomerular Filtration Barrier ◽  
Podocyte Injury ◽  
Nitrogen Levels ◽  
Filtration Barrier ◽  
Transmission Electron ◽  
High Level ◽  
Food Processes

Podocytes are a special type of differentiated epithelial cells that maintain the glomerular filtration barrier in the kidney. Injury or damages in podocytes can cause kidney-related disorders, like CKD. The injury or dysfunction of podocytes can occur by different metabolic disorders. Due to the severity and complexity of podocyte injuries, this state is considered as a serious health issue worldwide. Here, we examined and addressed the efficacy of an alternative Chinese medicine, Shen Qi Wan (SQW), on podocyte-related kidney injury. We evaluated the role and mechanism of action of SQW in podocyte injury. We observed that SQW significantly reduced 24-hour urinary protein and blood urea nitrogen levels and alleviated the pathological damage caused by adenine. Moreover, SQW significantly decreased the expression of nephrin and increased the expression of WT1 and AQP1 in the kidney of mice treated with adenine. We observed that SQW did not effectively reduce the high level of proteinuria in AQP1−/− mice indicating the prominent role of AQP1 in the SQW-ameliorating pathway. Transmission electron microscopy (TEM) images indicated the food processes effacement in AQP1−/− mice were not lessened by SQW. In conclusion, podocyte injury could alter the pathological nature of the kidney, and SQW administration relieves the nature of pathogenesis by activating AQP1.

scholarly journals Role of Supplementary Selenium on the Induction of Insulin Resistance and Oxidative Stress in NSY Mice Fed a High Fat Diet

2018 ◽  
Vol 41 (1) ◽  
pp. 92-98 ◽  
Author(s):  
Koichi Murano ◽  
Hirofumi Ogino ◽  
Tomofumi Okuno ◽  
Tomohiro Arakawa ◽  
Hitoshi Ueno
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
High Fat Diet ◽  
High Fat ◽  
And Oxidative Stress

Mo1016 Role of Oxidative Stress and Insulin Resistance in the Disease Severity of Non-Alcoholic Fatty Liver Disease

2013 ◽  
Vol 144 (5) ◽  
pp. S-1013
Author(s):  
Billur Canbakan ◽  
Hakan Senturk ◽  
Murat Tuncer ◽  
Ibrahim Hatemi ◽  
Emine Koroglu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Disease Severity ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Curcumin prevents inflammatory response, oxidative stress and insulin resistance in high fructose fed male Wistar rats: Potential role of serine kinases

2016 ◽  
Vol 244 ◽  
pp. 187-194 ◽  
Author(s):  
Nachimuthu Maithilikarpagaselvi ◽  
Magadi Gopalakrishna Sridhar ◽  
Rathinam Palamalai Swaminathan ◽  
Bobby Zachariah
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Inflammatory Response ◽  
Wistar Rats ◽  
Potential Role ◽  
High Fructose ◽  
Male Wistar Rats ◽  
Serine Kinases

scholarly journals OXIDATIVE STRESS AS THE PATHOPHYSIOLOGICAL MECHANISMS IN THE DEVELOPMENT OF DIABETIC MACROANGIOPATHY AND PERSPECTIVES OF ITS CORRECTION BY FLAVONOIDS

2016 ◽  
Vol 57 (3) ◽  
pp. 91-99
Author(s):  
N. I. Gorbenko ◽  
O. V. Ivanova ◽  
A. Y. Borikov
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Retrospective Analysis ◽  
Cardiometabolic Risk ◽  
Insulin Resistance Syndrome ◽  
Natural Antioxidants ◽  
Diabetic Macroangiopathy ◽  
Prevention And Treatment ◽  
Main Factors

The review elucidates the role of oxidative stress in the pathogenesis of diabetic cardiovascularcomplications. It was analyzed the main reasons for excessive production of reactive oxygen speciesin the conditions of hyperglycemia and the basic mechanisms of their damaging effect on the morphological and functional state of the myocardium and endothelium. It was considered theperspective of natural antioxidants, such as flavonoids, for the prevention and treatment of diabeticmacroangiopathy. It was made a retrospective analysis of own researches devoted to the quercetin effect on the main factors of cardiometabolic risk at the insulin resistance syndrome

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