scholarly journals Irbesartan Ameliorates Diabetic Nephropathy by Suppressing the RANKL-RANK-NF-κB Pathway in Type 2 Diabetic db/db Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Xiao-Wen Chen ◽  
Xiao-Yan Du ◽  
Yu-Xian Wang ◽  
Jian-Cheng Wang ◽  
Wen-Ting Liu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Glomerular Sclerosis ◽  
Protective Effects ◽  
Podocyte Injury ◽  
Beneficial Effects ◽  
Focal Segmental Glomerular Sclerosis ◽  
Receptor Activator ◽  
Segmental Glomerular Sclerosis ◽  
Type 2 Diabetic

The receptor activator of NF-κB ligand (RANKL) and its receptor RANK are overexpressed in focal segmental glomerular sclerosis (FSGS), IgA nephropathy (IgAN), and membranous nephropathy (MN). However, the expression and the potential roles of RANKL and RANK in diabetic nephropathy (DN) remain unclear. Irbesartan (Irb) has beneficial effects against diabetes-induced renal damage, but its mechanisms are poorly understood. Our present study investigated the effects of Irb in DN and whether the renal protective effects of Irb are mediated by RANKL/RANK and the downstream NF-κB pathway in db/db mice. Our results showed that db/db mice revealed severe metabolic abnormalities, renal dysfunction, podocyte injury, and increased MCP-1; these symptoms were reversed by Irb. At the molecular level, RANKL and RANK were overexpressed in the kidneys of db/db mice and Irb downregulated RANKL and RANK and inhibited the downstream NF-κB pathway. Our study suggests that Irb can ameliorate DN by suppressing the RANKL-RANK-NF-κB pathway.

scholarly journals Renal Podocyte Injury in a Rat Model of Type 2 Diabetes Is Prevented by Metformin

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Junghyun Kim ◽  
Eunjin Shon ◽  
Chan-Sik Kim ◽  
Jin Sook Kim
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Glycated Haemoglobin ◽  
Protective Effects ◽  
Podocyte Injury ◽  
Podocyte Loss ◽  
Renal Changes ◽  
Hypoglycemic Drug ◽  
Antioxidant Effects

Hyperglycemia promotes oxidative stress and hence generation of reactive oxygen species (ROS), which is known to play a crucial role in the pathogenesis of diabetic nephropathy. Metformin, an oral hypoglycemic drug, possesses antioxidant effects. The aim of this paper is to investigate the protective effects of metformin on the injury of renal podocytes in spontaneously diabetic Torii (SDT) rats, a new model for nonobese type 2 diabetes. Metformin (350 mg/kg/day) was given to SDT rats for 17 weeks. Blood glucose, glycated haemoglobin (HbA1c), and albuminuria were examined. Kidney histopathology, renal 8-hydroxydeoxyguanosine (8-OHdG) levels and apoptosis were examined. In 43-week-old SDT rats, severe hyperglycemia was developed, and albuminuria was markedly increased. Diabetes induced significant alterations in renal glomerular structure. In addition, urinary and renal 8-OHdG levels were highly increased, and podocyte loss was shown through application of the TUNEL and synaptopodin staining. However, treatment of SDT rats with metformin restored all these renal changes. Our data suggested that diabetes-induced podocyte loss in diabetic nephropathy could be suppressed by the antidiabetes drug, metformin, through the repression of oxidative injury.

scholarly journals Eleutheroside E, An Active Component ofEleutherococcus senticosus, Ameliorates Insulin Resistance in Type 2 Diabetic db/db Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Jiyun Ahn ◽  
Min Young Um ◽  
Hyunjung Lee ◽  
Chang Hwa Jung ◽  
Seok Hyun Heo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Uptake ◽  
Serum Insulin ◽  
Principal Component ◽  
C2c12 Myotubes ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Eleutheroside E ◽  
Type 2 Diabetic

Eleutheroside E (EE), a principal component ofEleutherococcus senticosus(ES), has anti-inflammatory and protective effects in ischemia heart. However, it is unknown whether it ameliorates insulin resistance and reduces hyperglycemia in diabetes. This study investigated the effect of EE-containing ES extracts, as well as EE, on hyperglycemia and insulin resistance in db/db mice. EE increased the insulin-provoked glucose uptake in C2C12 myotubes. Moreover, EE improved TNF-α-induced suppression of glucose uptake in 3T3-L1 adipocytes. Five-week-old db/db mice were fed a diet consisting of ES extract or EE for 5 weeks. Both were effective in improving serum lipid profiles and significantly decreased blood glucose and serum insulin levels. ES and EE supplementation effectively attenuated HOMA-IR. Glucose tolerance and insulin tolerance tests showed that EE increased insulin sensitivity. Immunohistochemical staining indicated that ES and EE protected pancreatic alpha and beta cells from diabetic damage. In addition, ES and EE improved hepatic glucose metabolism by upregulating glycolysis and downregulating gluconeogenesis in obese type 2 diabetic mice. These data suggest that EE mediates the hyperglycemic effects of ES by regulating insulin signaling and glucose utilization. The beneficial effects of EE may provide an effective and powerful strategy to alleviate diabetes.

Aliskiren enhances protective effects of valsartan against type 2 diabetic nephropathy in mice

2010 ◽  
Vol 28 (7) ◽  
pp. 1554-1565 ◽  
Author(s):  
Yi-Fei Dong ◽  
Lei Liu ◽  
Zhong-Fang Lai ◽  
Eiichiro Yamamoto ◽  
Keiichiro Kataoka ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Protective Effects ◽  
Type 2 Diabetic

Lipotoxicity dysregulates the immunoproteasome in podocytes and kidneys in type 2 diabetes

2021 ◽  
Vol 320 (4) ◽  
pp. F548-F558
Author(s):  
Hyun Soon Lee ◽  
Ji Yeon Suh ◽  
Byeong-Choel Kang ◽  
Eugene Lee
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Fish Oil ◽  
Olive Oil ◽  
Renal Cortex ◽  
Diabetic Mice ◽  
Podocyte Injury ◽  
Type 2 Diabetic

In podocytes, PA rapidly induced immunoproteasome expression but ultimately decreased it, while OA and EPA restored the decreased immunoproteasome levels. In the renal cortex of type 2 diabetic mice, immunoproteasome expression was significantly decreased, whereas feeding of OA-rich olive oil or EPA-rich fish oil diets protected them against the reduced immunoproteasome expression and progression of diabetic nephropathy. Thus, lipotoxicity-induced podocyte injury with impaired immunoproteasome expression may be related to the pathogenesis of diabetic nephropathy.

The SGLT2 inhibitor empagliflozin ameliorates early features of diabetic nephropathy in BTBR ob/ob type 2 diabetic mice with and without hypertension

2014 ◽  
Vol 307 (3) ◽  
pp. F317-F325 ◽  
Author(s):  
Florian Gembardt ◽  
Christoph Bartaun ◽  
Natalia Jarzebska ◽  
Eric Mayoux ◽  
Vladimir T. Todorov ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Sglt2 Inhibitor ◽  
Western World ◽  
Diabetic Mice ◽  
Antidiabetic Therapy ◽  
Beneficial Effects ◽  
Stage Renal Disease ◽  
Early Features ◽  
Type 2 Diabetic

Diabetic nephropathy is the leading cause of end-stage renal disease in humans in the Western world. The recent development of Na+-glucose cotransporter 2 (SGLT2) inhibitors offers a new antidiabetic therapy via enhanced glucose excretion. Whether this strategy exerts beneficial effects on the development of type 2 diabetic nephropathy is still largely unclear. We investigated the effects of the specific SGLT2 inhibitor empagliflozin in BTBR.Cg-Lep<ob>/WiscJ (BTBR ob/ ob) mice, which spontaneously develop type 2 diabetic nephropathy. In the first experiment, BTBR ob/ ob mice received either a diet containing 300 ppm empagliflozin or equicaloric placebo chow for 12 wk. In the second experiment, BTBR ob/ ob mice received 1 μg·kg body wt−1·day−1 ANG II to induce arterial hypertension and were separated into the same two diet groups for 6 wk. In both experiments, empagliflozin treatment enhanced glucosuria, thereby lowering blood glucose. Independently of hypertension, empagliflozin reduced albuminuria in diabetic mice. However, empagliflozin treatment affected diabetes-related glomerular hypertrophy, markers of renal inflammation, and mesangial matrix expansion only in BTBR ob/ ob mice without hypertension. In summary, empagliflozin demonstrated significant antihyperglycemic effects, differentially ameliorating early features of diabetic nephropathy in BTBR ob/ ob mice with and without hypertension.

scholarly journals Protective effects of alkali‐extracted rice protein on diabetic nephropathy in obese type 2 diabetic rats

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Masatoshi Kubota ◽  
Reiko Watanabe ◽  
Miki Yamaguchi ◽  
Michihiro Hosojima ◽  
Akihiko Saito ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Diabetic Rats ◽  
Protective Effects ◽  
Rice Protein ◽  
Type 2 Diabetic

scholarly journals The podocyte as a direct target for treatment of glomerular disease?

2016 ◽  
Vol 311 (1) ◽  
pp. F46-F51 ◽  
Author(s):  
Sandeep K. Mallipattu ◽  
John C. He
Keyword(s):  
The United States ◽  
Glomerular Disease ◽  
Glomerular Sclerosis ◽  
Systemic Effects ◽  
Glomerular Diseases ◽  
Podocyte Injury ◽  
Filtration Barrier ◽  
Focal Segmental Glomerular Sclerosis ◽  
Control And Prevention ◽  
Segmental Glomerular Sclerosis

The Centers for Disease Control and Prevention estimates more than 10% of adults in the United States, over 20 million Americans, have chronic kidney disease (CKD). A failure to maintain the glomerular filtration barrier directly contributes to the onset of CKD. The visceral epithelial cells, podocytes, are integral to the maintenance of this renal filtration barrier. Direct podocyte injury contributes to the onset and progression of glomerular diseases such as minimal change disease (MCD), focal segmental glomerular sclerosis (FSGS), diabetic nephropathy, and HIV-associated nephropathy (HIVAN). Since podocytes are terminally differentiated with minimal capacity to self-replicate, they are extremely sensitive to cellular injury. In the past two decades, our understanding of the mechanism(s) by which podocyte injury occurs has greatly expanded. With this newfound knowledge, therapeutic strategies have shifted to identifying targets directed specifically at the podocyte. Although the systemic effects of these agents are important, their direct effect on the podocyte proves to be essential in ameliorating glomerular disease. In this review, we highlight the mechanisms by which these agents directly target the podocyte independent of its systemic effects.

scholarly journals Protective Effects of Curcumin on Renal Oxidative Stress and Lipid Metabolism in a Rat Model of Type 2 Diabetic Nephropathy

2016 ◽  
Vol 57 (3) ◽  
pp. 664 ◽  
Author(s):  
Bo Hwan Kim ◽  
Eun Soo Lee ◽  
Ran Choi ◽  
Jarinyaporn Nawaboot ◽  
Mi Young Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Lipid Metabolism ◽  
Rat Model ◽  
Protective Effects ◽  
Type 2 Diabetic
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