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Pathogenesis diabetic nephropathy

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https://www.readbyqxmd.com/read/28214337/palmitate-induces-mitochondrial-superoxide-generation-and-activates-ampk-in-podocytes
#1
Eugene Lee, Jin Choi, Hyun Soon Lee
Studies have shown that high levels of serum free fatty acids (FFAs) are associated with lipotoxicity and type 2 diabetes. Palmitic acid (PA) is the predominant circulating saturated FFA, yet its role in the pathogenesis of diabetic nephropathy (DN) is not clear. Recently, one study suggested that mitochondrial superoxide production is related to AMP-activated protein kinase (AMPK) activity in diabetic mice kidneys. To elucidate the link between PA and oxidative stress and AMPK activity in DN, we compared the cultured murine podocytes exposed to PA and oleic acid (OA)...
February 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28208054/high-glucose-induced-hypomethylation-promotes-binding-of-sp-1-to-myo-inositol-oxygenase-implication-in-the-pathobiology-of-diabetic-tubulopathy
#2
Isha Sharma, Rajesh K Dutta, Neel K Singh, Yashpal S Kanwar
The catabolic enzyme myo-inositol oxygenase (MIOX) is expressed in proximal tubules and up-regulated in the diabetic state. Previously, we reported its transcriptional and translation regulation by high glucose (HG), osmolytes, and fatty acids. However, its epigenetic regulation is unknown. Bisulfite sequencing revealed that both human and mouse MIOX promoters, enriched with CpG sites, are hypomethylated and unmethylated under HG ambience and hyperglycemic states associated with increased MIOX expression. Eletrophoretic mobility shift assays revealed increased binding of unmethylated oligos with nucleoproteins of cells maintained under HG...
February 13, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28201968/common-drugs-for-stabilization-of-renal-function-in-the-progression-of-diabetic-nephropathy-and-their-relations-with-hypertension-therapy
#3
Yuxuan Wang, Chengcheng Wang, Xiuli Zhang, Harvest F Gu, Liang Wu
Diabetic nephropathy is characterized by hypertension, progressive albuminuria, glomerulosclerosis and declines in glomerular filtration rate leading to end stage renal disease. Although the pathogenesis of diabetic nephropathy is not fully understood, current treatment of the patients with diabetic nephropathy is mainly based upon the control of hyperglycaemia and management of blood pressures. Several drugs, which are originally developed for hypertension therapy, have been adopted for stabilization of renal function in diabetic nephropathy...
February 14, 2017: Current Diabetes Reviews
https://www.readbyqxmd.com/read/28182703/nephropathy-in-pparg-null-mice-highlights-ppar%C3%AE-systemic-activities-in-metabolism-and-in-the-immune-system
#4
Barbara Toffoli, Federica Gilardi, Carine Winkler, Magnus Soderberg, Laura Kowalczuk, Yvan Arsenijevic, Krister Bamberg, Olivier Bonny, Béatrice Desvergne
Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-dependent transcription factor involved in many aspects of metabolism, immune response, and development. Total-body deletion of the two Pparg alleles provoked generalized lipoatrophy along with severe type 2 diabetes. Herein, we explore the appearance and development of structural and functional alterations of the kidney, comparing Pparg null-mice to their littermate controls (carrying Pparg floxed alleles). We show that renal hypertrophy and functional alterations with increased glucosuria and albuminuria are already present in 3 weeks-old Pparg null-mice...
2017: PloS One
https://www.readbyqxmd.com/read/28181698/calcium-uptake-via-mitochondrial-uniporter-contributes-to-palmitic-acid-induced-apoptosis-in-mouse-podocytes
#5
Zeting Yuan, Aili Cao, Hua Liu, Henjiang Guo, Yingjun Zang, Yi Wang, Yunman Wang, Hao Wang, Peihao Yin, Wen Peng
Podocytes are component cells of the glomerular filtration barrier, and their loss by apoptosis is the main cause of proteinuria that leads to diabetic nephropathy (DN). Therefore, insights into podocyte apoptosis mechanism would allow a better understanding of DN pathogenesis and thus help develop adequate therapeutic strategies. Here, we investigated the molecular mechanism of palmitic acid-inhibited cell death in mouse podocytes, and found that palmitic acid increased cell death in a dose- and time-dependent manner...
February 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28178159/adma-predicts-major-adverse-renal-events-in-patients-with-mild-renal-impairment-and-or-diabetes-mellitus-undergoing-coronary-angiography
#6
Fabian Heunisch, Lyubov Chaykovska, Gina von Einem, Markus Alter, Thomas Dschietzig, Axel Kretschmer, Karl-Heinz Kellner, Berthold Hocher
Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of the nitric oxide (NO)-synthase and a biomarker of endothelial dysfunction (ED). ED plays an important role in the pathogenesis of contrast-induced nephropathy (CIN). The aim of our study was to evaluate serum ADMA concentration as a biomarker of an acute renal damage during the follow-up of 90 days after contrast medium (CM) application.Blood samples were obtained from 330 consecutive patients with diabetes mellitus or mild renal impairment immediately before, 24 and 48 hours after the CM application for coronary angiography...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28159318/circulating-fibronectin-contributes-to-mesangial-expansion-in-a-murine-model-of-type-1-diabetes
#7
Verena Klemis, Hiba Ghura, Giuseppina Federico, Carina Würfel, Anke Bentmann, Norbert Gretz, Tatsuhiko Miyazaki, Hermann-Joseph Gröne, Inaam A Nakchbandi
Fibronectin is ubiquitously expressed in the extracellular matrix, and its accumulation in the glomerular mesangium in diabetic nephropathy is associated with deterioration of renal function in these patients. However, the exact role of fibronectin in the pathogenesis of diabetic nephropathy remains unknown. To clarify this, we administered fluorescent-labeled plasma fibronectin to wild-type mice and found it to accumulate in the mesangium. Using liver-specific conditional-knockout mice to decrease circulating fibronectin, we reduced circulating fibronectin by more than 90%...
January 31, 2017: Kidney International
https://www.readbyqxmd.com/read/28137588/long-noncoding-rna-tgu1-alleviates-extracellular-matrix-accumulation-via-mediating-microrna-377-targeting-of-ppar%C3%AE-in-diabetic-nephropathy
#8
Min Ding, Li-Jun Hou, Qian Yu, Yun-Zhi Xing, Mei-Jun Wang, Ting-Wei Zhang, Peng-Hua Wang, De-Min Yu, Chun-Jun Li
Long noncoding RNA taurine-upregulated gene 1 (lncRNA TGU1) has been reported to play a key role in the progression of diabetic nephropathy (DN). However, the role of lncRNA TGU1 in the regulation of diabetic nephropathy remains largely unknown. The aim of the present study is to identify the regulation of lncRNA TGU1 on extracellular matrix accumulation via mediating microRNA-377 targeting of PPARγ, and investigate the underlying mechanisms in progression of DN. Microarray was performed to screen differentially expressed miRNAs in db/db DN mice...
January 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28134328/effect-of-bilirubin-concentration-on-the-risk-of-diabetic-complications-a-meta-analysis-of-epidemiologic-studies
#9
Bo Zhu, Xiaomei Wu, Yifei Bi, Yang Yang
Diabetes can affect many parts of the body and is associated with serious complications. Oxidative stress is a major contributor in the pathogenesis of diabetic complications and bilirubin has been shown to have antioxidant effects. The number of studies on the effect of bilirubin on the risk of diabetic complications has increased, but the results are inconsistent. Thus, we performed a meta-analysis to determine the relationship between bilirubin concentration and the risk of diabetic complications, and to investigate if there was a dose-response relationship...
January 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28123512/sirt4-overexpression-protects-against-diabetic-nephropathy-by-inhibiting-podocyte-apoptosis
#10
Jian-Xia Shi, Qi-Jin Wang, Hui Li, Qin Huang
Diabetic nephropathy is a diabetic complication associated with capillary damage and increased mortality. Sirtuin 4 (SIRT4) plays an important role in mitochondrial function and the pathogenesis of metabolic diseases, including aging kidneys. The aim of the present study was to investigate the association between SIRT4 and diabetic nephropathy in a glucose-induced mouse podocyte model. A CCK-8 assay showed that glucose simulation significantly inhibited podocyte proliferation in a time- and concentration-dependent manner...
January 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28105508/euterpe-oleracea-mart-seed-extract-protects-against-renal-injury-in-diabetic-and-spontaneously-hypertensive-rats-role-of-inflammation-and-oxidative-stress
#11
Viviane da Silva Cristino Cordeiro, Graziele Freitas de Bem, Cristiane Aguiar da Costa, Izabelle Barcellos Santos, Lenize Costa Reis Marins de Carvalho, Dayane Teixeira Ognibene, Ana Paula Machado da Rocha, Jorge José de Carvalho, Roberto Soares de Moura, Angela Castro Resende
PURPOSE: Euterpe oleracea Mart. (açaí) seed extract (ASE), through its anti-hypertensive, antioxidant and anti-inflammatory properties, may be useful to treat or prevent human diseases. Several evidences suggest that oxidative stress and inflammation contribute to the pathogenesis of diabetic nephropathy; therefore, we tested the hypothesis that ASE (200 mg/kg(-1)day(-1)) prevents diabetes and hypertension-related oxidative stress and inflammation, attenuating renal injury. METHODS: Male rats with streptozotocin (STZ)-induced diabetes (D), and spontaneously hypertensive rats with STZ-induced diabetes (DH) were treated daily with tap water or ASE (D + ASE and DH + ASE, respectively) for 45 days...
January 20, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28007334/microarray-analysis-of-long-noncoding-rna-expression-patterns-in-diabetic-nephropathy
#12
Sheng Chen, Chenglong Dong, Xiaoxiao Qian, Shanshan Huang, Yamin Feng, Xiaolong Ye, Heng Miao, Qiang You, Yibing Lu, Dafa Ding
AIMS: Long noncoding RNAs (lncRNAs) are implicated in various biological processes and human diseases. Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). We explored the potential functions of lncRNAs in DN. METHODS: We established a mouse model of DN and compared lncRNA expression patterns between DN model and db/m control mouse kidney tissues using microarray analysis. lncRNA function was predicted by gene ontology enrichment and KEGG pathway analyses of lncRNAs-coexpressed mRNAs...
December 8, 2016: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28001175/nodular-glomerulosclerosis-in-a-non-diabetic-hypertensive-dyslipidemic-smoker-patient-a-case-report
#13
Liliane Silvano Araújo, Alessandro Alves Queiroz, Maria Luíza Reis Monteiro, Crislaine Aparecida Silva, Lívia Helena de Morais Pereira, Mariana Molinar Mauad Cintra, Claudia Renata Bibiano Borges, Juliana Reis Machado, Marlene Antônia Dos Reis
INTRODUCTION: This is a case report of a patient with idiopathic nodular glomerulosclerosis whose pathogenesis and morphology are similar to diabetic nephropathy. CASE PRESENTATION: A 64-year-old Brazilian man, leukoderma, dyslipidemic, obese with chronic obstructive pulmonary disease secondary to tobacco smoking, known to be hypertensive for five years and he had no history of diabetes. He was admitted with sudden anasarca, rapid loss of renal function and needed to start hemodialysis immediately...
December 2016: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
https://www.readbyqxmd.com/read/27993541/diabetes-microvascular-complications-a-clinical-update
#14
REVIEW
H Khalil
BACKGROUND: The purpose of this study is to summarise the empirical evidence addressing diabetes microvascular complications and management. The effects of diabetes mellitus include long-term damage, dysfunction and failure of various organs. Microvascular disease tends to occur predominantly in tissues where glucose uptake is independent of insulin activity because these tissues are exposed to glucose levels that correlate very closely with blood glucose levels. These metabolic injuries cause altered blood flow and changes in endothelial permeability, extravascular protein deposition and coagulation resulting in organ dysfunction which in turn lead to microvascular complications...
December 13, 2016: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/27976371/apolipoprotein-c-i-plays-a-role-in-the-pathogenesis-of-glomerulosclerosis
#15
Pascal Bus, Louise Pierneef, Rosalie Bor, Ron Wolterbeek, Leendert A van Es, Patrick C N Rensen, Emile de Heer, Louis M Havekes, Jan A Bruijn, Jimmy F Berbée, Hans J Baelde
Diabetic nephropathy is the leading cause of end-stage renal disease. Diabetic patients have increased plasma concentrations of apolipoprotein C-I (apoCI), and meta-analyses found that a polymorphism in APOC1 is associated with an increased risk of developing nephropathy. To investigate whether overexpressing apoCI contributes to the development of kidney damage, we studied renal tissue and peritoneal macrophages from APOC1 transgenic (APOC1-tg) mice and wild-type littermates. In addition, we examined renal autopsy material from diabetic patients with and without diabetic nephropathy and from control subjects...
December 15, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27964927/long-noncoding-rna-malat1-regulates-renal-tubular-epithelial-pyroptosis-by-modulated-mir-23c-targeting-of-elavl1-in-diabetic-nephropathy
#16
Xue Li, Li Zeng, Chuanwu Cao, Chenhui Lu, Weishuai Lian, Jianhong Han, Xiaojun Zhang, Jing Zhang, Tao Tang, Maoquan Li
Diabetic nephropathy is a common kidney condition in patients with diabetes mellitus, which can result in renal failure. Pyroptosis, the process of pro-inflammatory programmed cell death, plays an important role in the pathogenesis of this disease. Long non-coding RNA MALAT1 has also been shown to be involved in diabetic nephropathy. Here, we investigated the role of MALAT1 and the microRNA miR-23c and its target gene ELAVL1 in renal tubular epithelial cells. Our data demonstrated that MALAT1 expression was substantially increased but miR-23c was decreased in streptozotocin-induced diabetic rats and in high-glucose-treated HK-2 cells...
December 10, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27904696/a-study-on-the-correlation-between-mthfr-promoter-methylation-and-diabetic-nephropathy
#17
Xiao-Hui Yang, Ren-Fang Cao, Yang Yu, Miao Sui, Tao Zhang, Jing-Yi Xu, Xiao-Mei Wang
OBJECTIVE: In order to observe the relationship between MTHFR promoter and DN, the determinations on MTHFR promoter methylation level and expression of HCY from DN patients have been carried out. METHODS: According to the Diabetes diagnosis and classification standard from WHO in 1999, 85 patients with DM diagnosed by Endocrinology and 30 healthy participants from our medical examination center were chosen as control specimen to study in this paper. All this specimen were divided into A, B, C and D four groups , which are corresponding simple diabetes mellitus group (SDM), early diabetic nephropathy group (EDN), clinical diabetic nephropathy group (CDN) and normal control group...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27882943/metadherin-facilitates-podocyte-apoptosis-in-diabetic-nephropathy
#18
Wen-Ting Liu, Fen-Fen Peng, Hong-Yu Li, Xiao-Wen Chen, Wang-Qiu Gong, Wen-Jing Chen, Yi-Hua Chen, Pei-Lin Li, Shu-Ting Li, Zhao-Zhong Xu, Hai-Bo Long
Apoptosis, one of the major causes of podocyte loss, has been reported to have a vital role in diabetic nephropathy (DN) pathogenesis, and understanding the mechanisms underlying the regulation of podocyte apoptosis is crucial. Metadherin (MTDH) is an important oncogene, which is overexpressed in most cancers and responsible for apoptosis, metastasis, and poor patient survival. Here we show that the expression levels of Mtdh and phosphorylated p38 mitogen-activated protein kinase (MAPK) are significantly increased, whereas those of the microRNA-30 family members (miR-30s) are considerably reduced in the glomeruli of DN rat model and in high glucose (HG)-induced conditionally immortalized mouse podocytes (MPC5)...
November 24, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27881924/rodent-models-of-diabetic-nephropathy-their-utility-and-limitations
#19
REVIEW
Munehiro Kitada, Yoshio Ogura, Daisuke Koya
Diabetic nephropathy is the most common cause of end-stage renal disease. Therefore, novel therapies for the suppression of diabetic nephropathy must be developed. Rodent models are useful for elucidating the pathogenesis of diseases and testing novel therapies, and many type 1 and type 2 diabetic rodent models have been established for the study of diabetes and diabetic complications. Streptozotocin (STZ)-induced diabetic animals are widely used as a model of type 1 diabetes. Akita diabetic mice that have an Ins2+/C96Y mutation and OVE26 mice that overexpress calmodulin in pancreatic β-cells serve as a genetic model of type 1 diabetes...
2016: International Journal of Nephrology and Renovascular Disease
https://www.readbyqxmd.com/read/27874055/the-coordinated-roles-of-mir-26a-and-mir-30c-in-regulating-tgf%C3%AE-1-induced-epithelial-to-mesenchymal-transition-in-diabetic-nephropathy
#20
Zongji Zheng, Meiping Guan, Yijie Jia, Dan Wang, Ruoyu Pang, Fuping Lv, Zhizhou Xiao, Ling Wang, Hongbin Zhang, Yaoming Xue
MicroRNAs (miRNAs) play vital roles in the development of diabetic nephropathy. Here, we compared the protective efficacies of miR-26a and miR-30c in renal tubular epithelial cells (NRK-52E) and determined whether they demonstrated additive effects in the attenuation of renal fibrosis. TGFβ1 suppressed miR-26a and miR-30c expression but up-regulated pro-fibrotic markers in NRK-52E cells, and these changes were also found in the kidney cortex of 40-week-old diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats...
November 22, 2016: Scientific Reports
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