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Mechanisms renal damage diabetes

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https://www.readbyqxmd.com/read/28819999/high-glucose-induces-hgf-independent-activation-of-met-receptor-in-human-renal-tubular-epithelium
#1
Lucia Mesarosova, Peter Ochodnicky, Jaklien C Leemans, Sandrine Florquin, Peter Krenek, Jan Klimas
CONTEXT: The role of hepatocyte growth factor (HGF) in diabetic kidney damage remains controversial. OBJECTIVE: To test the hypothesis that high glucose levels activate pathways related to HGF and its receptor Met and that this could participate in glucose-induced renal cell damage. MATERIALS AND METHODS: HK2 cells, a human proximal tubule epithelial cell line, were stimulated with high glucose for 48 hours. Levels of pMet/Met, pEGFR/EGFR, pSTAT3/STAT3, pAkt/Akt and pERK1/2/ERK1/2 were studied by immunoblotting...
August 18, 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28805677/endocytosis-of-albumin-induces-matrix-metalloproteinase-9-by-activating-the-erk-signaling-pathway-in-renal-tubule-epithelial-cells
#2
Xiaoming Chen, Alyssa Cobbs, Jasmine George, Ashmeer Chima, Fidele Tuyishime, Xueying Zhao
Matrix metalloproteinase-9 (MMP-9) is dysregulated in chronic kidney diseases including diabetic nephropathy. This study was performed to examine the expression of MMP-9 in renal tubule epithelial cells (TECs) under diabetic conditions and its regulatory mechanisms. We characterized MMP-9 protein in diabetic animals and primary cultured rat TECs exposed to exogenous albumin and high glucose. We also used specific inhibitors to determine if internalization of albumin and/or extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation were required for MMP-9 secretion...
August 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28802226/taraxerol-a-pentacyclic-triterpenoid-from-abroma-augusta-leaf-attenuates-diabetic-nephropathy-in-type-2-diabetic-rats
#3
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...
August 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28791309/research-progress-on-mechanism-of-podocyte-depletion-in-diabetic-nephropathy
#4
REVIEW
Haoran Dai, Qingquan Liu, Baoli Liu
Diabetic nephropathy (DN) together with glomerular hyperfiltration has been implicated in the development of diabetic microangiopathy in the initial stage of diabetic diseases. Increased amounts of urinary protein in DN may be associated with functional and morphological alterations of podocyte, mainly including podocyte hypertrophy, epithelial-mesenchymal transdifferentiation (EMT), podocyte detachment, and podocyte apoptosis. Accumulating studies have revealed that disruption in multiple renal signaling pathways had been critical in the progression of these pathological damages, such as adenosine monophosphate-activated kinase signaling pathways (AMPK), wnt/β-catenin signaling pathways, endoplasmic reticulum stress-related signaling pathways, mammalian target of rapamycin (mTOR)/autophagy pathway, and Rho GTPases...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28750927/fibroblast-growth-factor-1-ameliorates-diabetic-nephropathy-by-an-anti-inflammatory-mechanism
#5
Guang Liang, Lintao Song, Zilu Chen, Yuanyuan Qian, Junjun Xie, Longwei Zhao, Qian Lin, Guanghui Zhu, Yi Tan, Xiaokun Li, Moosa Mohammadi, Zhifeng Huang
Inflammation plays a central role in the etiology of diabetic nephropathy, a global health issue. We observed a significant reduction in the renal expression of fibroblast growth factor 1, a known mitogen and insulin sensitizer, in patients with diabetic nephropathy and in mouse models implying that fibroblast growth factor 1 possesses beneficial anti-inflammatory and renoprotective activities in vivo. To test this possibility, we investigated the effects of chronic i.p. administration of fibroblast growth factor 1 into both the streptozotocin-induced type 1 diabetes and db/db type 2 diabetes models...
July 24, 2017: Kidney International
https://www.readbyqxmd.com/read/28728079/probucol-ameliorates-renal-injury-in-diabetic-nephropathy-by-inhibiting-the-expression-of-the-redox-enzyme-p66shc
#6
Shikun Yang, Li Zhao, Yachun Han, Yu Liu, Chao Chen, Ming Zhan, Xiaofen Xiong, Xuejing Zhu, Li Xiao, Chun Hu, Fuyou Liu, Zhiguang Zhou, Yashpal S Kanwar, Lin Sun
AIMS: Probucol is an anti-hyperlipidemic agent and a potent antioxidant drug that can delay progression of diabetic nephropathy (DN) and reverses renal oxidative stress in diabetic animal models; however, the mechanisms underlying these effects remain unclear. p66Shc is a newly recognized mediator of mitochondrial ROS production in renal cells under high-glucose (HG) ambience. We previously showed that p66Shc can serve as a biomarker for renal oxidative injury in DN patients and that p66Shc up-regulation is correlated with renal damage in vivo and in vitro...
July 4, 2017: Redox Biology
https://www.readbyqxmd.com/read/28719912/crocin-protects-podocytes-against-oxidative-stress-and-inflammation-induced-by-high-glucose-through-inhibition-of-nf-%C3%AE%C2%BAb
#7
Sutong Li, Xiaoxia Liu, Jie Lei, Junle Yang, Puxun Tian, Yi Gao
BACKGROUND/AIMS: Diabetic nephropathy (DN) is a microangiopathic disease characterized by excessive urinary albumin excretion, which occurs in 30% of patients with diabetes mellitus. It is the second leading cause of end-stage renal diseases in China. Nuclear factor-kappa B (NF-κB) is reported to be closely correlated with the inflammation underlying diabetes-associated renal damage. Crocin, a plant-derived compound, has antioxidant properties that may inhibit NF-κB. METHODS: In the present study, we used a conditionally immortalized mouse podocyte cell line to explore whether crocin could effectively block albuminuria...
July 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28708885/pioglitazone-ameliorates-glomerular-nlrp3-inflammasome-activation-in-apolipoprotein-e-knockout-mice-with-diabetes-mellitus
#8
Yao Wang, Bo Yu, Li Wang, Ming Yang, Zhiyin Xia, Wei Wei, Fengyu Zhang, Xiaochen Yuan
OBJECTIVE: The NLRP3 inflammasome plays an important role in the pathogenesis of inflammation in diabetic nephropathy (DN). Pioglitazone (PIO) has been found to exert an anti-inflammatory effect in patients with diabetes mellitus, but it is still unclear whether PIO exhibits a similar effect in DN. We aimed to explore the effect and underlying mechanism of PIO on DN, as well as investigate if NLRP3 is a pharmacologic target of PIO. METHODS: We divided 48 apolipoprotein E (apoE) (-/-) mice into 4 groups: apoE (-/-), apoE (-/-) with PIO, diabetic apoE (-/-), and diabetic apoE (-/-) with PIO...
2017: PloS One
https://www.readbyqxmd.com/read/28662169/antidiabetic-activities-of-polysaccharides-separated-from-inonotus-obliquus-via-the-modulation-of-oxidative-stress-in-mice-with-streptozotocin-induced-diabetes
#9
Juan Wang, Wenji Hu, Lanzhou Li, Xinping Huang, Yange Liu, Di Wang, Lirong Teng
This study evaluated the effects of Inonotus obliquus polysaccharides (IOs) on diabetes and other underlying mechanisms related to inflammatory factors and oxidative stress in a mouse model of streptozotocin (STZ)-induced diabetes. Four weeks administration of metformin (120 mg/kg) and IO1-4 (50%-80% alcohol precipitation), or IO5 (total 80% alcohol precipitation) at doses of 50 mg/kg reverses the abnormal changes of bodyweights and fasting blood glucose levels of diabetic mice. IOs significantly increased the insulin and pyruvate kinase levels in serum, and improved the synthesis of glycogen, especially for IO5...
2017: PloS One
https://www.readbyqxmd.com/read/28648975/effect-of-extract-of-pueraria-tuberosa-on-expression-of-hypoxia-inducible-factor-1%C3%AE-and-vascular-endothelial-growth-factor-in-kidney-of-diabetic-rats
#10
Rashmi Shukla, Nidhi Pandey, Somanshu Banerjee, Yamini B Tripathi
BACKGROUNDS: Kidney hypoxia represents a unifying mechanism in the pathogenesis of diabetic nephropathy. Hypoxia-induced factor (HIF)-1α mediates the metabolic responses of renal hypoxia by modulating the expression of VEGF. In the present study, we investigated the effect of Pueraria tuberosa extract (PTY-2r) on the expression of HIF-1α, VEGF and nephrin in streptozotocin (STZ) induced diabetic nephropathy (DN). METHODS: The model of diabetic nephropathy (DN) was produced by intraperitoneal injection of 55mg/kg of STZ and maintained for 60days...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28643849/prevalence-of-exposure-of-heavy-metals-and-their-impact-on-health-consequences
#11
Kanwal Rehman, Fiza Fatima, Iqra Waheed, Muhammad Sajid Hamid Akash
Even in the current era of growing technology, the concentration of heavy metals present in drinking water is still not within the recommended limits as set by the regulatory authorities in different countries of the world. Drinking water contaminated with heavy metals namely; arsenic, cadmium, nickel, chromium, mercury, chromium, zinc and lead is becoming a major health concern for public and health care professionals. Occupational exposure to heavy metals is known to occur by the utilization of these metals in various industrial processes and/or contents including color pigments and alloys...
June 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28642201/combination-of-coenzyme-q10-loaded-liposomes-with-ultrasound-targeted-microbubbles-destruction-utmd-for-early-theranostics-of-diabetic-nephropathy
#12
Ting Yue, He-Lin Xu, Pian-Pian Chen, Lei Zheng, Qun Huang, Wen-Shuang Sheng, Yuan-Di Zhuang, Li-Zhuo Jiao, Ting-Ting Chi, De-Li ZhuGe, Jin-Jin Liu, Ying-Zheng Zhao, Li Lan
Diabetic nephropathy (DN) is one of the most common and lethal microvascular complications of diabetes. This study aimed to explore whether coenzymeQ10 (CoQ10) as an antioxidant combined with ultrasound-targeted microbubble destruction (UTMD) could reverse the progress of early diabetic nephropathy (DN). CoQ10 has great potential to treat early DN. However, the clinical application of CoQ10 has been limited because of its low aqueous solubility and non-specific distribution. Therefore, CoQ10-loaded liposomes (CoQ10-lip) were prepared and combined with ultrasound microbubbles for the early theranostics of DN...
August 7, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28633927/dencichine-ameliorates-kidney-injury-in-induced-type-ii-diabetic-nephropathy-via-the-tgf-%C3%AE-smad-signalling-pathway
#13
Li Jie, Qiu Pengcheng, He Qiaoyan, Bi Linlin, Zhang Meng, Wang Fang, Jia Min, Yan Li, Zhang Ya, Yang Qian, Wang Siwang
Diabetic nephropathy (DN), a common complication associated with both type I and type II diabetes mellitus (DM), is a major cause of chronic nephropathy and a common cause of end-stage renal diseases (ESRD) throughout the world. This study is aimed to determine whether dencichine (De) can ameliorate renal damage in high-glucose-and-fat diet combined STZ (streptozocin) induced DN in type II DM rats and to investigate the potential underlying mechanisms. Markers of metabolism, diabetes, and renal function, and levels of extracellular matrix (ECM) collagen I (Col I), collagen IV (Col IV), fibronectin (FN) and laminin (LN), and of proteins in the TGF-β/Smad pathway were analysed through RT-PCR, western blot, immunofluorescence and immunohistochemistry...
June 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28624831/chelerythrine-attenuates-renal-ischemia-reperfusion-induced-myocardial-injury-by-activating-cse-h2s-via-pkc-nf-%C3%AE%C2%BAb-pathway-in-diabetic-rats
#14
Bo Hu, Guangtao Xu, Yongxia Zheng, Fei Tong, Ping Qian, Xiaoyan Pan, Xinmei Zhou, Ruilin Shen
BACKGROUND/AIMS: Chelerythrine (CHE), a benzophenanthridine alkaloid, is a potent, selective, and cell-permeable protein kinase C (PKC) inhibitor. The purpose of the present study was to evaluate the effect of CHE on myocardial recovery after renal ischemia/reperfusion (I/R)-induced myocardial injury (RI/RMI) in a streptozocin (STZ)-induced diabetic rat model. METHODS: Diabetes mellitus (DM) rats preconditioned with CHE and D, L-propargylglycine (PAG) were subjected to renal I/R...
2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/28624830/activation-of-nrf2-ho-1-pathway-by-glycogen-synthase-kinase-3%C3%AE-inhibition-attenuates-renal-ischemia-reperfusion-injury-in-diabetic-rats
#15
Xiaohua Shen, Bo Hu, Guangtao Xu, Fengjuan Chen, Ruifen Ma, Nenghua Zhang, Jie Liu, Xiaoqin Ma, Jia Zhu, Yuhong Wu, Ruilin Shen
BACKGROUND/AIMS: Diabetes mellitus can exacerbate renal ischemia-reperfusion (I/R) injury (RI/RI). The aim of the present study was to evaluate the protective effect of GSK-3β inhibition (TDZD-8) on I/R-induced renal injury through the Nrf2/HO-1 pathway in a streptozocin (STZ)-induced diabetic rat model. METHODS: STZ-induced diabetic rats preconditioned with TDZD-8 and ZnPP were subjected to renal I/R. The extent of renal morphologic lesions. Renal function was assessed from blood urea nitrogen (BUN) and serum creatinine (Scr), as determined utlizing commercial kits...
2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/28594240/dimethylarginine-dimethylaminohydrolase-1-deficiency-induces-the-epithelial-to-mesenchymal-transition-in-renal-proximal-tubular-epithelial-cells-and-exacerbates-kidney-damage-in-aged-and-diabetic-mice
#16
Linlin Shi, Chenyang Zhao, Hongyun Wang, Tong Lei, Shasha Liu, Jianwei Cao, Zhongbing Lu
AIMS: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is mainly degraded by dimethylarginine dimethylaminohydrolase (DDAH). Emerging evidence suggests that plasma ADMA accumulation and DDAH1 activity/expression reduction are linked to chronic kidney disease (CKD) pathology, but the mechanisms remain largely unknown. Here, we examined the role of ADMA/DDAH1 in the epithelial-mesenchymal transition (EMT) of tubular epithelial cells (TECs), an important mechanism for the pathogenesis of renal fibrosis...
July 7, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28593900/phellinus-rimosus-improves-mitochondrial-energy-status-and-attenuates-nephrotoxicity-in-diabetic-rats
#17
K A Rony, T A Ajith, Tony A Kuttikadan, R Blaze, K K Janardhanan
BACKGROUND: Mitochondrial dysfunction and increase in reactive oxygen species during diabetes can lead to pathological consequences in kidneys. The present study was aimed to investigate the effect of Phellinus rimosus in the streptozotocin (STZ)-induced diabetic rat renal mitochondria and the possible mechanism of protection. METHODS: Phellinus rimosus (50 and 250 mg/kg, p.o) was treated after inducing diabetes by STZ (45 mg/kg, i.p) in rats. The serum samples were subjected to creatinine and urea estimation...
April 7, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/28588189/metabolic-injury-induced-nlrp3-inflammasome-activation-dampens-phospholipid-degradation
#18
Elena Rampanelli, Evelyn Orsó, Peter Ochodnicky, Gerhard Liebisch, Pieter J Bakker, Nike Claessen, Loes M Butter, Marius A van den Bergh Weerman, Sandrine Florquin, Gerd Schmitz, Jaklien C Leemans
The collateral effects of obesity/metabolic syndrome include inflammation and renal function decline. As renal disease in obesity can occur independently of hypertension and diabetes, other yet undefined causal pathological pathways must be present. Our study elucidate novel pathological pathways of metabolic renal injury through LDL-induced lipotoxicity and metainflammation. Our in vitro and in vivo analysis revealed a direct lipotoxic effect of metabolic overloading on tubular renal cells through a multifaceted mechanism that includes intralysosomal lipid amassing, lysosomal dysfunction, oxidative stress, and tubular dysfunction...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28543864/modulation-of-heme-oxygenase-1-expression-and-activity-affects-streptozotocin-induced-diabetic-nephropathy-in-rats
#19
Marwa A M Ali, Gehan H Heeba, Azza A K El-Sheikh
Heme oxygenase (HO)-1 has exhibited nephro-protective actions in different animal models; however, its full mechanistic potential in diabetic nephropathy (DN) has not yet been elucidated. Hence, the present study has been undertaken by inducing DN in rats using streptozotocin (50mg/kg i.p.), with or without either HO-1 inducer; hemin (HM; 40 μmol/kg, s.c.), or HO-1 blocker; zinc protoporphyrin-IX (ZnPP; 50 μmol/kg, i.p.), for one month. Compared to control, rats with DN suffered from hyperglycemia and hyperlipidemia, with signs of renal damage, as assessed by distortion in renal histopathological architecture and kidney function...
May 23, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28496544/hemodynamic-effects-of-sodium-glucose-cotransporter-2-inhibitors
#20
REVIEW
Motoaki Sano
It is widely accepted that obesity and type 2 diabetes mellitus (T2DM) increase the risk of heart failure (HF) independently of underlying coronary artery disease. The changes in myocardial structure or function associated with diabetes have been termed diabetic cardiomyopathy. Corresponding to changes in the risk factors for HF, an epidemiologic transition is underway from HF with a reduced ejection fraction to HF with a preserved ejection fraction. Hyperglycemia can damage the myocardium, even before diagnosis of diabetes, but intensive glycemic control has no impact on the risk of HF in patients with T2DM...
June 2017: Journal of Clinical Medicine Research
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