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 Additive protection by LDR and FGF21 treatment against diabetic nephropathy in type 2 diabetes model

2015 ◽  
Vol 309 (1) ◽  
pp. E45-E54 ◽  
Author(s):  
Minglong Shao ◽  
Lechu Yu ◽  
Fangfang Zhang ◽  
Xuemian Lu ◽  
Xiaokun Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Combination Treatment ◽  
Combined Treatment ◽  
Protective Effects ◽  
Diabetic Mice ◽  
Renal Protection ◽  
Glucose Levels

The onset of diabetic nephropathy (DN) is associated with both systemic and renal changes. Fibroblast growth factor (FGF)-21 prevents diabetic complications mainly by improving systemic metabolism. In addition, low-dose radiation (LDR) protects mice from DN directly by preventing renal oxidative stress and inflammation. In the present study, we tried to define whether the combination of FGF21 and LDR could further prevent DN by blocking its systemic and renal pathogeneses. To this end, type 2 diabetes was induced by feeding a high-fat diet for 12 wk followed by a single dose injection of streptozotocin. Diabetic mice were exposed to 50 mGy LDR every other day for 4 wk with and without 1.5 mg/kg FGF21 daily for 8 wk. The changes in systemic parameters, including blood glucose levels, lipid profiles, and insulin resistance, as well as renal pathology, were examined. Diabetic mice exhibited renal dysfunction and pathological abnormalities, all of which were prevented significantly by LDR and/or FGF21; the best effects were observed in the group that received the combination treatment. Our studies revealed that the additive renal protection conferred by the combined treatment against diabetes-induced renal fibrosis, inflammation, and oxidative damage was associated with the systemic improvement of hyperglycemia, hyperlipidemia, and insulin resistance. These results suggest that the combination treatment with LDR and FGF21 prevented DN more efficiently than did either treatment alone. The mechanism behind these protective effects could be attributed to the suppression of both systemic and renal pathways.

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.

scholarly journals Is Podocyte Injury Relevant in Diabetic Nephropathy?: Studies in Patients With Type 2 Diabetes

Diabetes ◽  
2003 ◽  
Vol 52 (4) ◽  
pp. 1031-1035 ◽  
Author(s):  
M. Dalla Vestra ◽  
A. Masiero ◽  
A. M. Roiter ◽  
A. Saller ◽  
G. Crepaldi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Podocyte Injury

scholarly journals Metformin use associated with protective effects for ocular complications in patients with type 2 diabetes – observational study

2018 ◽  
Vol 46 (2) ◽  
pp. 116
Author(s):  
Sanita Maleškić ◽  
Jasna Kusturica ◽  
Edis Gušić ◽  
Maida Rakanović-Todić ◽  
Damir Šečić ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Diabetic Retinopathy ◽  
Medical Records ◽  
Glycated Haemoglobin ◽  
Protective Effects ◽  
Ocular Complications ◽  
Oral Antihyperglycemic Agents ◽  
Antihyperglycemic Agents

<div class="WordSection1"><p><strong>Objective. </strong>The aim was to study the association of the use of an oral antihyperglycemic agent metformin with the presence of ocular complications in patients with type 2 diabetes (T2D). <strong>Methods. </strong>Medical records were reviewed for 234 patients with diagnosed T2D. 81.2% (n=190) patients were using metformin and 18.8% (n=44) using other oral antihyperglycemic agents. Plasma glucose concentration, glycated haemoglobin, and the presence of ocular complications in patients treated with metformin were compared to those in patients treated with other oral antihyperglycemic agents. <strong>Results. </strong>Ocular complications occurred in 65 patients (27.8%). Patients treated with metformin had fewer ocular complications compared to patients treated with other oral antihyperglycemic agents (χ2=19.985; p&lt;0.0001). After adjustment for gender, age, duration of T2D, serum concentration of cholesterol, smoking, body mass index and presence of other diseases, treatment with metformin decreased <strong>the</strong> odds of both glaucoma (OR=0.14, 95% CI: 0.03-0.57, p=0.006) and diabetic retinopathy (OR=0.33, 95% CI: 0.14-0.82, p=0.017) compared with other oral antihyperglycemic agents. <strong>Conclusion. </strong>Our results suggest that metformin may have a protective effect on ocular complications, especially glaucoma, in patients with T2D. The effects of metformin either regarding prevention of ocular complications or ocular complications already developed in patients with T2D, should be further investigated.</p></div>

scholarly journals Lower Plasma Creatinine and Urine Albumin in Individuals at Increased Risk of Type 2 Diabetes with Factor V Leiden Mutation

2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
Andreas Peter ◽  
Andreas Fritsche ◽  
Fausto Machicao ◽  
Peter P. Nawroth ◽  
Hans-Ulrich Häring ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Factor V Leiden ◽  
Plasma Creatinine ◽  
Factor V ◽  
Protective Effects ◽  
Lower Plasma ◽  
Urine Albumin ◽  
Fvl Mutation

The factor V Leiden (FVL) mutation is the most frequent genetic cause of venous thrombosis in Caucasians. However, protective effects have been suggested to balance the disadvantages. We have recently observed protective effects of FVL mutation on experimental diabetic nephropathy in mice as well as an association with reduced albuminuria in two human cohorts of diabetic patients. In the present study we aimed to reevaluate these findings in an independent, larger cohort of 1905 Caucasians at risk of developing type 2 diabetes and extend possible associations to earlier disease stages of nephropathy. Carriers of FVL mutation had a significantly lower urine albumin excretion (P=0.03) and tended to have lower plasma creatinine concentrations (P=0.07). The difference in plasma creatinine concentrations was significant after adjustment for the influencing factors: age, gender, and lean body mass (P=0.048). These observations at a very early “disease” stage are an important extension of previous findings and suggest that modification of glomerular dysfunction by FVL mutation is relevant during very early stages of diabetic nephropathy. This makes the underlying mechanism an interesting therapeutic target and raises the question whether FVL mutation may also exert protective effects in other glomerulopathies.

Valsartan slows the progression of diabetic nephropathy in db/db mice via a reduction in podocyte injury, and renal oxidative stress and inflammation

2014 ◽  
Vol 126 (10) ◽  
pp. 707-720 ◽  
Author(s):  
Guangyu Zhou ◽  
Alfred K. Cheung ◽  
Xia Liu ◽  
Yufeng Huang
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Podocyte Injury

Valsartan, given at a dose that reduces proteinuria, maximally slows the progression of the renal structural lesions resulting from Type 2 diabetes in db/db mice via protection of renal podocytes and a reduction in renal oxidative stress and inflammation.

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 SGLT2 Inhibitors for Treatment of Diabetic Nephropathy

2019 ◽  
Vol 12 (3) ◽  
Author(s):  
Nasser Mikhail
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Primary Outcome ◽  
Sglt2 Inhibitors ◽  
Drug Discontinuation ◽  
Protective Effects ◽  
Renal Protection ◽  
Ras Blockers

Background: Sodium-glucose co-transporter 2 (SGLT2) are medications approved for treatment of type 2 diabetes. Recent evidence suggests that these agents exert Reno protective effects. Methods: Review of literature (English, French, Spanish) from January 1990 to November 10, 2019. Searching terms include sodium-glucose co-transporters 2 inhibitors (SGLT2) inhibitors, chronic kidney disease (CKD), end-stage kidney disease (ESKD). Randomized trials, meta-analysis, expert opinions and guidelines are also reviewed. Results: The effects of canagliflozin on renal events were evaluated in patients with type 2 diabetes and albuminuric diabetic nephropathy already on renin-angiotensin (RAS) blockade. The primary outcome was a composite of the incidence of ESKD, doubling of serum creatinine, renal or cardiovascular (CV) death. Canagliflozin was associated with 30% reduction in the incidence of this primary outcome [hazard ratio (HR) 0.70, 95% CI 0.59-0.82, P=0.00001)]. Similar results were generally reported in large CV trials of canagliflozin, empagliflozin and dapagliflozin although renal events were secondary or post-hoc outcomes. Renoprotection by SGLT2 inhibitors was observed in patients with different degrees of renal function at baseline, with or without albuminuria, and taking or not RAS blockers. SGLT2 inhibitors were generally safe with drug discontinuation rates similar to placebo. Canagliflozin was tolerated in patients with eGFR <60 ml/min/1.73 m2. The incidence of acute renal injury was numerically less frequent with SGLT2 inhibitors compared with placebo. Conclusions: SGLT2 inhibitors slow progression of diabetic nephropathy and should be standard of care on top of RAS blockers for renal protection in patients with type 2 diabetes. Regulatory authorities should consider allowing using canagliflozin 100 mg/d in patients with estimated glomerular filtration rate (eGFR) between 30-45 ml/min/1.73 m2./p>

scholarly journals The role of metformin in the prevention of diabetic nephropathy in experimental type 2 diabetes

2016 ◽  
Vol 15 (3) ◽  
pp. 70-80
Author(s):  
V. K. Bayrasheva ◽  
A. Yu. Babenko ◽  
Yu. V. Dmitriev ◽  
A. A. Bairamov ◽  
S. G. Chefu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Microvascular Complications ◽  
Kidney Injury ◽  
Tubular Damage ◽  
Metformin Treatment ◽  
Protective Effects ◽  
Metformin Therapy ◽  
Kidney Injury Molecule 1

Introduction and purpose. A number of landmark trials have demonstrated clear benefits of metformin therapy in the prevention of macrovascular outcomes. Nevertheless, there is a lack of robust evidence to suggest whether metformin therapy will have similar beneficial outcomes in one of the most serious type 2 diabetes-related renal microvascular complications known as diabetic nephropathy. The study aimed to evaluate the effects of ten-week metformin treatment on renal morphofunctional changes in rats with non-genetic type 2 diabetic nephropathy. Materials and methods. Starting at 3 weeks after unilateral nephrectomy, adult male Wistar rats were fed the high-fat diet for 5 weeks, and then successively received nicotinamide (230 mg/kg) and streptozotocin (65 mg/kg) intraperitoneally in 15-min interval. Results. Starting at 11 weeks after confirmation of diabetes, metformin treatment did not attenuate routine renal dysfunction markers such as creatinine, creatinine clearance and albuminuria compared to placebo-treated diabetic group, and glomerulosclerosis index and glomerular expression of type IV collagen didn't significantly change either. Nevertheless, level of urinary kidney injury molecule-1, considered to be the marker of tubular damage in diabetes, was significantly lower in metformin-treated animals. Moreover, reduction of tubulointerstitial lesion tended to be significant. Conclusions. Under conditions of diabetic nephropathy modeling, metformin has shown direct protective effects against diabetic tubular disturbance. To assess long-term renal outcomes of these findings, more pre-clinical studies and clinical trials are required.

scholarly journals Taurine Alleviates the Progression of Diabetic Nephropathy in Type 2 Diabetic Rat Model

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Jang Hyun Koh ◽  
Eun Soo Lee ◽  
Miri Hyun ◽  
Hong Min Kim ◽  
Yoon Jung Choi ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Insulin Secretion ◽  
Glucose Level ◽  
Rat Model ◽  
Diabetic Rat ◽  
Control Group ◽  
Protective Effects ◽  
Oletf Rats ◽  
Antioxidant Effects

The overexpression of vascular endothelial growth factor (VEGF) is known to be involved in the pathogenesis of diabetic nephropathy. In this study, the protective effects of taurine on diabetic nephropathy along with its underlying mechanism were investigated. Experimental animals were divided into three groups: LETO rats as normal group (n=10), OLETF rats as diabetic control group (n=10), and OLETF rats treated with taurine group (n=10). We treated taurine (200 mg/kg/day) for 20 weeks and treated high glucose (HG, 30 mM) with or without taurine (30 mM) in mouse cultured podocyte. After taurine treatment, blood glucose level was decreased and insulin secretion was increased. Taurine significantly reduced albuminuria and ACR. Also it decreased glomerular volume, GBM thickness and increased open slit pore density through decreased VEGF and increased nephrin mRNA expressions in renal cortex. The antioxidant effects of taurine were confirmed by the reduction of urine MDA in taurine treated diabetic group. Also reactive oxygen species (ROS) levels were decreased in HG condition with taurine treated podocytes compared to without taurine. These results indicate that taurine lowers glucose level via increased insulin secretion and ameliorates the progression of diabetic nephropathy through antifibrotic and antioxidant effects in type 2 diabetes rat model.

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