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Pathogenesis diabetic nephropathy

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https://www.readbyqxmd.com/read/28912302/prevention-of-renal-apob-retention-is-protective-against-diabetic-nephropathy-role-of-tgf-%C3%AE-inhibition
#1
Patricia G Wilson, Joel C Thompson, Meghan H Yoder, Richard Charnigo, Lisa R Tannock
Animal studies demonstrate that hyperlipidemia and renal lipid accumulation contribute to the pathogenesis of diabetic nephropathy. We previously demonstrated that renal lipoproteins co-localize with biglycan, a renal proteoglycan. The purpose of this study was to determine if prevention of renal lipid (apoB) accumulation attenuates diabetic nephropathy. Biglycan deficient and biglycan wildtype Ldlr-/- mice were made diabetic via streptozotocin and fed a high cholesterol diet. As biglycan deficiency is associated with elevated TGF-b, in some experiments mice were injected with either the TGF-b neutralizing antibody 1D11 or with 13C4, an irrelevant control antibody...
September 14, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28904427/micrornas-involvement-in-renal-pathophysiology-a-bird-s-eye-view
#2
REVIEW
P Jaswani, S Prakash, A Dhar, R K Sharma, N Prasad, S Agrawal
MicroRNAs (miRNAs) are known to suppress gene expression by binding to messenger RNAs and in turn regulate different pathophysiological processes. Transforming growth factor-β, mitogen-activated protein kinase signaling, and Wnt signaling-like major pathways associated with miRNAs are involved with kidney diseases. The discovery of miRNAs has provided new insights into kidney pathologies and may provide effective therapeutic strategies. Research has demonstrated the role of miRNAs in a variety of kidney diseases including diabetic nephropathy, lupus nephritis, hypertension, nephritic syndrome, acute kidney injury, renal cell carcinoma, and renal fibrosis...
September 2017: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/28881810/infiltrating-macrophages-in-diabetic-nephropathy-promote-podocytes-apoptosis-via-tnf-%C3%AE-ros-p38mapk-pathway
#3
Yinfeng Guo, Zhixia Song, Min Zhou, Ying Yang, Yu Zhao, Bicheng Liu, Xiaoliang Zhang
Macrophage infiltration has been linked to the pathogenesis of diabetic nephropathy (DN). However, how infiltrating macrophages affect the progression of DN is unknown. Although infiltrating macrophages produce pro-inflammatory mediators and induce apoptosis in a variety of target cells, there are no studies in podocytes. Therefore, we tested the contribution of macrophages to podocytes apoptosis in DN. in vivo experiments showed that apoptosis in podocytes was increased in streptozocin (STZ)-induced diabetic rats compared with control rats and that this apoptosis was accompanied by increased macrophages infiltration in the kidney...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28875851/urotensin-ii-molecular-mechanisms-of-biological-activity
#4
Andrey A Svistunov, Vadim V Tarasov, Svetlana A Shakhmardanova, Susanna S Sologova, Ekaterina T Bagaturija, Vladimir N Chubarev, Pavel A Galenko-Yaroshevsky, George E Barreto, Gjumrakch Aliev
Urotensin II (UT II) is an important factor of cellular homeostasis. This regulatory peptide is involved in the pathophysiology of many disorders. For example, it plays an important role in the pathogenesis of acute and chronic diseases, stressful and adaptive reactions of the body, in the development of cardiovascular pathologies, metabolic syndrome, inflammation, liver cirrhosis, renal failure, diabetic nephropathy, reproductive dysfunction, progression of psychosomatic, psychoendocrinal and psychiatric disorders...
August 29, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28871454/non-genetic-mechanisms-of-diabetic-nephropathy
#5
REVIEW
Qiuxia Han, Hanyu Zhu, Xiangmei Chen, Zhangsuo Liu
Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetes mellitus patients and is characterized by thickened glomerular basement membrane, increased extracellular matrix formation, and podocyte loss. These phenomena lead to proteinuria and altered glomerular filtration rate, that is, the rate initially increases but progressively decreases. DN has become the leading cause of end-stage renal disease. Its prevalence shows a rapid growth trend and causes heavy social and economic burden in many countries...
September 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28864059/role-of-omentin-1-and-il-6-in-type-2-diabetes-mellitus-patients-with-diabetic-nephropathy
#6
Gandhipuram Periyasamy Senthilkumar, Melepallappil Sabeenakumari Anithalekshmi, Md Yasir, Sreejith Parameswaran, Rajaa Muthu Packirisamy, Zachariah Bobby
AIMS: Diabetic nephropathy (DN) is one of the major chronic vascular complication of T2DM and leading cause of end-stage renal disease. Inflammation is one of the proposed pathway which explains microvascular complications in T2DM but exact mechanism is still unclear. Omentin-1 is an anti-inflammatory adipokine which promotes insulin signaling. IL-6 is a multifunctional cytokine having role in immune and inflammatory responses. The present study was conducted to elucidate the role of omentin-1 and IL-6 in the pathogenesis of DN and its association with insulin resistance...
August 24, 2017: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/28860538/sirt1-rs10823108-and-foxo1-rs17446614-responsible-for-genetic-susceptibility-to-diabetic-nephropathy
#7
Yanyan Zhao, Junfang Wei, Xuefeng Hou, Huimiao Liu, Feng Guo, Yingni Zhou, Yuanyuan Zhang, Yunhui Qu, Junfei Gu, Yuanli Zhou, Xiaobin Jia, Guijun Qin, Liang Feng
SIRT1 and FOXO1 play an important role in the pathogenesis of diabetic nephropathy (DN). However, the association between genetic polymorphisms and susceptibility to type 2 DN (T2DN) has not been explored. In this study, a total of 1066 patients with type 2 diabetes mellitus (T2DM) (413 without and 653 with DN) were enrolled. The genotypes of three htSNPs (rs3818292, rs4746720, rs10823108) within SIRT1 and two htSNPs (rs2721068, rs17446614) in FOXO1 were determined by PCR-RFLP. HbA1C, LDL, HDL, TC, and TG levels were also examined...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28860163/proximal-tubular-cannabinoid-1-receptor-regulates-obesity-induced-ckd
#8
Shiran Udi, Liad Hinden, Brian Earley, Adi Drori, Noa Reuveni, Rivka Hadar, Resat Cinar, Alina Nemirovski, Joseph Tam
Obesity-related structural and functional changes in the kidney develop early in the course of obesity and occur independently of hypertension, diabetes, and dyslipidemia. Activating the renal cannabinoid-1 receptor (CB1R) induces nephropathy, whereas CB1R blockade improves kidney function. Whether these effects are mediated via a specific cell type within the kidney remains unknown. Here, we show that specific deletion of CB1R in the renal proximal tubule cells did not protect the mice from obesity, but markedly attenuated the obesity-induced lipid accumulation in the kidney and renal dysfunction, injury, inflammation, and fibrosis...
August 31, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28853522/-the-effect-of-vitamin-d-on-the-expression-of-adamts13-in-cultured-endothelial-cells-exposed-to-a-diabetic-like-environment
#9
Keren Cohen-Hagai, Gloria Rashid, Meital Ohana, Sydney Benchetrit, Tali Zitman-Gal
BACKGROUND: Diabetes mellitus (DM) is the leading cause of end-stage kidney disease. Inflammation, fibrosis, coagulability and oxidative stress exacerbate kidney disease. The glycoprotein, Von Willebrand Factor (VWF) has a crucial role in platelet thrombus formation. The enzyme ADAMTS13 is responsible for VWF cleavage. Both are important in the interface between diabetic nephropathy, hypercoagulability and atherosclerotic cardiovascular disease. Vitamin D inhibits endothelial proliferation, blunts angiogenesis and is a cardioprotective agent...
August 2017: Harefuah
https://www.readbyqxmd.com/read/28845600/implications-of-impaired-zinc-homeostasis-in-diabetic-cardiomyopathy-and-nephropathy
#10
REVIEW
Robertina Giacconi, Lu Cai, Laura Costarelli, Maurizio Cardelli, Marco Malavolta, Francesco Piacenza, Mauro Provinciali
Impaired zinc homeostasis is observed in diabetes mellitus (DM2) and its complications. Zinc has a specific role in pancreatic β-cells via insulin synthesis, storage, and secretion. Intracellular zinc homeostasis is tightly controlled by zinc transporters (ZnT and Zip families) and metallothioneins (MT) which modulate the uptake, storage, and distribution of zinc. Several investigations in animal models demonstrate the protective role of MT in DM2 and its cardiovascular or renal complications, while a copious literature shows that a common polymorphism (R325W) in ZnT8, which affects the protein's zinc transport activity, is associated with increased DM2 risk...
August 27, 2017: BioFactors
https://www.readbyqxmd.com/read/28840540/a-more-tubulocentric-view-of-diabetic-kidney-disease
#11
REVIEW
Letizia Zeni, Anthony G W Norden, Giovanni Cancarini, Robert J Unwin
Diabetic nephropathy (DN) is a common complication of Diabetes Mellitus (DM) Types 1 and 2, and prevention of end stage renal disease (ESRD) remains a major challenge. Despite its high prevalence, the pathogenesis of DN is still controversial. Initial glomerular disease manifested by hyperfiltration and loss of glomerular size and charge permselectivity may initiate a cascade of injuries, including tubulo-interstitial disease. Clinically, 'microalbuminuria' is still accepted as an early biomarker of glomerular damage, despite mounting evidence that its predictive value for DN is questionable, and findings that suggest the proximal tubule is an important link in the development of DN...
August 24, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28802226/taraxerol-a-pentacyclic-triterpenoid-from-abroma-augusta-leaf-attenuates-diabetic-nephropathy-in-type-2-diabetic-rats
#12
Ritu Khanra, Niloy Bhattacharjee, Tarun K Dua, Ashis Nandy, Achintya Saha, Jatin Kalita, Prasenjit Manna, Saikat Dewanjee
Persistent hyperglycaemia coupled with inflammation plays an important role in the pathogenesis of diabetic nephropathy (DN). Present study examined the therapeutic potential of taraxerol isolated from the methanol extract of Abroma augusta leaf against DN using rodent model of type 2 diabetes (T2D). T2D was experimentally induced by high fat diet and a single low-single dose of streptozotocin (35mg/kg, i.p.). Accumulation of serum creatinine, urea, and uric acid, activation of lactate dehydrogenase and creatinin kinase, and release of urinary albumin represented the glomerular damage and the progression of nephropathy in T2D rats...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28798291/function-of-nlrp3-in-the-pathogenesis-and-development-of-diabetic-nephropathy
#13
Ying Fu, Nannan Wu, Dong Zhao
BACKGROUND The aim of this research was to study the function of NLRP3 in the pathogenesis and development of diabetic nephropathy (DN). MATERIAL AND METHODS We compared the expression of NLRP3-related protein in human glomerular mesangial cells under high glucose conditions at different times and in rats with DN of different ages. We also compared changes in IL-18 and IL-1β expression levels at different stages of DN. RESULTS After six hours, 12 hours, and 24 hours of high glucose stimulation, the secretion of IL-1β in human glomerular mesangial cells, compared to unstimulated cells, was 1...
August 11, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28759755/the-roles-of-sodium-glucose-cotransporter-2-inhibitors-in-preventing-kidney-injury-in-diabetes
#14
REVIEW
Krit Jaikumkao, Anchalee Pongchaidecha, Varanuj Chatsudthipong, Siriporn C Chattipakorn, Nipon Chattipakorn, Anusorn Lungkaphin
Diabetic nephropathy (DN) is the leading cause of end stage renal disease (ESRD) worldwide. The early effective treatment of high plasma glucose could delay or prevent the onset of DN. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are new target treatments for ameliorating high plasma glucose and help to maintain glucose homeostasis in diabetic patients. Reduced renal glucose reabsorption by SGLT2 inhibition seems to have high potential to improve glycemic control in diabetes mellitus (DM) not only through glucose lowering but also through glucose-independent effects such as blood pressure-lowering and direct renal effects in diabetes...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28758590/renin-angiotensin-system-in-diabetes
#15
Michael Bader, Johannes Rein
The renin-angiotensin system (RAS) has two different axes, the classical one with the effector peptide angiotensin II and the new one with the effector peptide angiotensin (1-7). Both peptides have been shown to be involved in the pathogenesis of diabetes mellitus and its consequences, nephropathy, retinopathy and cardiomyopathy in animal models and patients. Angiotensin II acts mostly in a deleterious fashion and angiotensin (1-7) in a protective fashion. In this review we summarize the knowledge about the role of the different RAS axes in diabetes mellitus and the use of drugs interfering with the RAS in the therapy of the disease...
July 28, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28757338/soluble-epoxide-hydrolase-in-podocytes-is-a-significant-contributor-to-renal-function-under-hyperglycemia
#16
Ahmed Bettaieb, Shinichiro Koike, Ming-Fo Hsu, Yoshihiro Ito, Samah Chahed, Santana Bachaalany, Artiom Gruzdev, Miguel Calvo-Rubio, Kin Sing Stephen Lee, Bora Inceoglu, John D Imig, Jose M Villalba, Darryl C Zeldin, Bruce D Hammock, Fawaz G Haj
BACKGROUND: Diabetic nephropathy (DN) is the leading cause of renal failure, and podocyte dysfunction contributes to the pathogenesis of DN. Soluble epoxide hydrolase (sEH, encoded by Ephx2) is a conserved cytosolic enzyme whose inhibition has beneficial effects on renal function. The aim of this study is to investigate the contribution of sEH in podocytes to hyperglycemia-induced renal injury. MATERIALS AND METHODS: Mice with podocyte-specific sEH disruption (pod-sEHKO) were generated, and alterations in kidney function were determined under normoglycemia, and high-fat diet (HFD)- and streptozotocin (STZ)-induced hyperglycemia...
July 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28754553/real-time-in%C3%A2-vivo-mitochondrial-redox-assessment-confirms-enhanced-mitochondrial-reactive-oxygen-species-in-diabetic-nephropathy
#17
Daniel L Galvan, Shawn S Badal, Jianyin Long, Benny H Chang, Paul T Schumacker, Paul A Overbeek, Farhad R Danesh
While increased mitochondrial reactive oxygen species have been commonly implicated in a variety of disease states, their in vivo role in the pathogenesis of diabetic nephropathy remains controversial. Using a two-photon imaging approach with a genetically encoded redox biosensor, we monitored mitochondrial redox state in the kidneys of experimental models of diabetes in real-time in vivo. Diabetic (db/db) mice that express a redox-sensitive Green Fluorescent Protein biosensor (roGFP) specifically in the mitochondrial matrix (db/dbmt-roGFP) were generated, allowing dynamic monitoring of redox changes in the kidneys...
July 26, 2017: Kidney International
https://www.readbyqxmd.com/read/28748185/novel-actions-of-growth-hormone-in-podocytes-implications-for-diabetic-nephropathy
#18
REVIEW
Dhanunjay Mukhi, Rajkishor Nishad, Ram K Menon, Anil Kumar Pasupulati
The kidney regulates water, electrolyte, and acid-base balance and thus maintains body homeostasis. The kidney's potential to ensure ultrafiltered and almost protein-free urine is compromised in various metabolic and hormonal disorders such as diabetes mellitus (DM). Diabetic nephropathy (DN) accounts for ~20-40% of mortality in DM. Proteinuria, a hallmark of renal glomerular diseases, indicates injury to the glomerular filtration barrier (GFB). The GFB is composed of glomerular endothelium, basement membrane, and podocytes...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28744992/the-effect-of-12-weeks-carnosine-supplementation-on-renal-functional-integrity-and-oxidative-stress-in-pediatric-patients-with-diabetic-nephropathy-a-randomized-placebo-controlled-trial
#19
Nancy Samir Elbarbary, Eman Abdel Rahman Ismail, Abdel Rahman El-Naggar, Mahitab Hany Hamouda, Manal El-Hamamsy
BACKGROUND AND OBJECTIVES: Oxidative stress is a significant contributor to the pathogenesis of diabetic nephropathy. Carnosine is a natural radical oxygen species scavenger. We investigated the effect of carnosine as an adjuvant therapy on urinary albumin excretion (UAE), the tubular damage marker alpha 1-microglobulin (A1M), and oxidative stress in pediatric patients with type 1 diabetes and nephropathy. METHODS: This randomized placebo-controlled trial included 90 patients with diabetic nephropathy, despite oral angiotensin-converting enzyme inhibitors (ACE-Is), who were randomly assigned to receive either 12 weeks of carnosine 1 g/day (n = 45), or matching placebo (n = 45)...
July 26, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28743882/hyperoside-pre-treatment-prevents-glomerular-basement-membrane-damage-in-diabetic-nephropathy-by-inhibiting-podocyte-heparanase-expression
#20
Xiaofei An, Lin Zhang, Yanggang Yuan, Bin Wang, Qiuming Yao, Ling Li, Jisheng Zhang, Ming He, Jinan Zhang
Glomerular basement membrane (GBM) damage plays a pivotal role in pathogenesis of albuminuria in diabetic nephropathy (DN). Heparan sulfate (HS) degradation induced by podocyte heparanase is the major cause of GBM thickening and abnormal perm-selectivity. In the present study, we aimed to examine the prophylactic effect of hyperoside on proteinuria development and GBM damage in DN mouse model and the cultured mouse podocytes. Pre-treatment with hyperoside (30 mg/kg/d) for four weeks could significantly decrease albuminuria, prevent GBM damage and oxidative stress in diabetes mellitus (DM) mice...
July 25, 2017: Scientific Reports
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