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Diabetic nephropathy Tubule

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https://www.readbyqxmd.com/read/27916082/-effects-of-ammonium-pyrrolidine-dithiocarbamate-pdtc-on-osteopontin-expression-and-autophagy-in-tubular-cells-in-streptozotocin-induced-diabetic-nephropathy-rat
#1
S Gao, J Y Jia, T K Yan, Y M Yu, W Y Shang, L Wei, Z F Zheng, P Fang, B C Chang, S Lin
Objective: To investigate the effects of ammonium pyrrolidine dithiocarbamate (PDTC) on tubulointerstitial inflammatory molecules and autophagy in diabetic nephropathy (DN) rats. Methods: Twenty-four male Sprague-Dawley rats were assigned to DN group (n=6) and DN+ PDTC group (n=6, PDTC, ip, 100 mg·kg(-1)·d(-1)), all received streptozotocin (STZ) 60 mg/kg intraperitoneally, and the other 12 rats were randomly divided into control group (n=6) and PDTC group (n=6). At the end of 12 weeks, after serum creatine (Scr) and 24-hour urinary protein were determined, rats were sacrificed to determined the renal pathological damages and the changes of nuclear factor (NF)-κB p65, p62, osteopontin (OPN), microtubule associated protein 1 light chain 3 (LC3)-Ⅱ/LC3-Ⅰ, nuclear p-NF-κB p65 by immunohistological stainning and Western blot, and ultrastructural changes of autophagic process was observed by electron microscopy (EM)...
November 29, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27849017/elmo1-protects-renal-structure-and-ultrafiltration-in-kidney-development-and-under-diabetic-conditions
#2
Krishna Rakesh Sharma, Karl Heckler, Sandra J Stoll, Jan-Luuk Hillebrands, Katharina Kynast, Esther Herpel, Stefan Porubsky, Marlies Elger, Boris Hadaschik, Karen Bieback, Hans-Peter Hammes, Peter P Nawroth, Jens Kroll
Engulfment and cell motility 1 (ELMO1) functions as a guanine exchange factor for Rac1 and was recently found to protect endothelial cells from apoptosis. Genome wide association studies suggest that polymorphisms within human elmo1 act as a potential contributing factor for the development of diabetic nephropathy. Yet, the function of ELMO1 with respect to the glomerulus and how this protein contributes to renal pathology was unknown. Thus, this study aimed to identify the role played by ELMO1 in renal development in zebrafish, under hyperglycaemic conditions, and in diabetic nephropathy patients...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27798458/the-angiotensin-type-2-receptor-and-the-kidney
#3
Antonio A B Peluso, Robson A S Santos, Thomas Unger, U Muscha Steckelings
PURPOSE OF REVIEW: Angiotensin II is a main regulator of kidney function. Renal actions mediated by the angiotensin AT1 receptor have been well known for many years. In contrast, several details of angiotensin AT2 receptor actions in kidney physiology and pathophysiology were only described very recently. These findings are reviewed in this article. RECENT FINDINGS: Regarding the role of the angiotensin AT2 receptor in kidney physiology, a major recent finding was that the AT2 receptor-mediated inhibition of Na-H exchanger-3 and Na/K-ATPase in the renal proximal tubules is caused by internalisation of these transporters, thus reducing reabsorption and increasing natriuresis/diuresis...
January 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/27777973/systems-biology-analysis-reveals-role-of-mdm2-in-diabetic-nephropathy
#4
Rintaro Saito, Anaïs Rocanin-Arjo, Young-Hyun You, Manjula Darshi, Benjamin Van Espen, Satoshi Miyamoto, Jessica Pham, Minya Pu, Simone Romoli, Loki Natarajan, Wenjun Ju, Matthias Kretzler, Robert Nelson, Keiichiro Ono, Dana Thomasova, Shrikant R Mulay, Trey Ideker, Vivette D'Agati, Ergin Beyret, Juan Carlos Izpisua Belmonte, Hans Joachim Anders, Kumar Sharma
To derive new insights in diabetic complications, we integrated publicly available human protein-protein interaction (PPI) networks with global metabolic networks using metabolomic data from patients with diabetic nephropathy. We focused on the participating proteins in the network that were computationally predicted to connect the urine metabolites. MDM2 had the highest significant number of PPI connections. As validation, significant downregulation of MDM2 gene expression was found in both glomerular and tubulointerstitial compartments of kidney biopsy tissue from 2 independent cohorts of patients with diabetic nephropathy...
October 20, 2016: JCI Insight
https://www.readbyqxmd.com/read/27771693/kidney-injury-marker-1-and-neutrophil-gelatinase-associated-lipocalin-in-chronic-kidney-disease
#5
Esmeralda Castillo-Rodriguez, Raul Fernandez-Prado, Catalina Martin-Cleary, Maria Soledad Pizarro-Sánchez, Maria Dolores Sanchez-Niño, Ana Belen Sanz, Beatriz Fernandez-Fernandez, Alberto Ortiz
The current categorization of chronic kidney disease (CKD) is based on biomarkers of the glomerular function (estimated glomerular filtration rate, eGFR) and injury (urinary albumin creatinine ratio, UACR) and provides information on the risk of death and of progression of kidney disease. However, there are gaps in knowledge regarding the risk stratification of elderly patients with eGFR 45-60 ml/min/1.73 m2 and of younger patients with higher eGFR but physiological albuminuria. In this regard, most of the kidney cell mass is composed of tubules...
October 22, 2016: Nephron
https://www.readbyqxmd.com/read/27757071/n-glycosylation-proteome-enrichment-analysis-in-kidney-reveals-differences-between-diabetic-mouse-models
#6
Leena Liljedahl, Maiken Højgaard Pedersen, Jenny Norlin, James N McGuire, Peter James
BACKGROUND: Diabetic nephropathy (DN) is a late complication in both type 1 diabetes mellitus (T1DM) and T2DM. Already at an early stage of DN morphological changes occur at the cell surface and in the extracellular matrix where the majority of the proteins carry N-linked glycosylations. These glycosylated proteins are highly important in cell adhesion and cell-matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances...
2016: Clinical Proteomics
https://www.readbyqxmd.com/read/27754252/os-36-03-e-box-cpg-hypomethylation-of-nmn-producing-enzyme-nampt-in-proximal-tubules-enables-constant-supply-of-nmn-from-tubules-to-glomeruli-which-is-disrupted-in-diabetic-nephropathy
#7
Hirokazu Muraoka, Kazuhiro Hasegawa, Shu Wakino
OBJECTIVE: Nicotinamide phosphoribosyltransferase (Nampt) cooperates with a longevity gene, Sirt1, to exert the potentiation of stress resistance. We have reported that the high expression level of Nampt in PTs contributes to the sufficient supply of NMN to glomeruli. We also showed that downregulation of Nampt and NMN in PT in DN leads to glomerular damages (Nature Medicine 2013). However, the regulation mechanisms of Nampt expression remain unknown. DESIGN AND METHOD: We investigated how Nampt expression is consistently retained at high levels in PTs under normal conditions and how Nampt levels are decreased in DN...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27669287/tauroursodeoxycholic-acid-attenuates-renal-tubular-injury-in-a-mouse-model-of-type-2-diabetes
#8
Jing Zhang, Ying Fan, Chuchu Zeng, Li He, Niansong Wang
Renal tubular injury is a critical factor in the pathogenesis of diabetic nephropathy (DN). Endoplasmic reticulum (ER) stress is involved in diabetic nephropathy. Tauroursodeoxycholic acid (TUDCA) is an effective inhibitor of ER stress. Here, we investigated the role of TUDCA in the progression of tubular injury in DN. For eight weeks, being treated with TUDCA at 250 mg/kg intraperitoneal injection (i.p.) twice a day, diabetic db/db mice had significantly reduced blood glucose, albuminuria and attenuated renal histopathology...
2016: Nutrients
https://www.readbyqxmd.com/read/27643217/os-36-03-e-box-cpg-hypomethylation-of-nmn-producing-enzyme-nampt-in-proximal-tubules-enables-constant-supply-of-nmn-from-tubules-to-glomeruli-which-is-disrupted-in-diabetic-nephropathy
#9
Hirokazu Muraoka, Kazuhiro Hasegawa, Shu Wakino
OBJECTIVE: Nicotinamide phosphoribosyltransferase (Nampt) cooperates with a longevity gene, Sirt1, to exert the potentiation of stress resistance. We have reported that the high expression level of Nampt in PTs contributes to the sufficient supply of NMN to glomeruli. We also showed that downregulation of Nampt and NMN in PT in DN leads to glomerular damages (Nature Medicine 2013). However, the regulation mechanisms of Nampt expression remain unknown. DESIGN AND METHOD: We investigated how Nampt expression is consistently retained at high levels in PTs under normal conditions and how Nampt levels are decreased in DN...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27591880/effect-of-linagliptin-on-structural-changes-in-the-kidney-in-experimental-type-2-diabetes-mellitus
#10
Yu S Gavrilova, N P Bgatova, V V Klimontov, I Yu Ischenko, S V Michurina, N E Myakina, E L Zavyalov
Effect of the dipeptidyl peptidase-4 inhibitor linagliptin on structural manifestations of diabetic nephropathy was studied in BKS.Cg-Dock7m+/+Leprdb/J mice (experimental model of type 2 diabetes mellitus). Linagliptin (10 mg/kg per day) or vehicle was administered by gavage over 8 weeks. Mesangial expansion, thickening of the basement membrane in glomerular capillaries and proximal tubules, and retraction of cytopodia were less pronounced in mice receiving linagliptin. The protective effect of linagliptin on the kidney structure was not associated with its hypoglycemic action...
August 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27470548/sirt1-activator-ameliorates-the-renal-tubular-injury-induced-by-hyperglycemia-in-vivo-and-in-vitro-via-inhibiting-apoptosis
#11
Xue-Ling Wang, Li-Yan Wu, Long Zhao, Li-Na Sun, Hai-Ying Liu, Gang Liu, Guang-Ju Guan
We aimed to explore the role of SIRT1 in apoptosis in human kidney proximal tubule epithelial (HK-2) cells, and to determine whether resveratrol (RSV, a SIRT1 activator) could ameliorate apoptosis in rats with streptozotocin-induced diabetes mellitus (DM) and/or in high glucose (HG, 30mM) - stimulated HK-2 cells. Rats were distributed randomly into three groups: 1) control group, 2) DM group, and 3) DM with RSV group (DM+RSV; rats treated with 30mg/kg/d of RSV for 16 weeks). The physical, biochemical, and morphological parameters were then examined...
June 21, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27440829/sglt2-inhibitors-and-the-diabetic-kidney
#12
Paola Fioretto, Alberto Zambon, Marco Rossato, Luca Busetto, Roberto Vettor
Diabetic nephropathy (DN) is the most common cause of end-stage renal disease worldwide. Blood glucose and blood pressure control reduce the risk of developing this complication; however, once DN is established, it is only possible to slow progression. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, the most recent glucose-lowering oral agents, may have the potential to exert nephroprotection not only through improving glycemic control but also through glucose-independent effects, such as blood pressure-lowering and direct renal effects...
August 2016: Diabetes Care
https://www.readbyqxmd.com/read/27388219/nmda-receptors-as-potential-therapeutic-targets-in-diabetic-nephropathy-increased-renal-nmda-receptor-subunit-expression-in-akita-mice-and-reduced-nephropathy-following-sustained-treatment-with-memantine-or-mk-801
#13
Hila Roshanravan, Eun Young Kim, Stuart E Dryer
N-methyl-d-aspartate (NMDA) receptors are expressed throughout the kidney, and the abundance of these receptors and some of their endogenous agonists are increased in diabetes. Moreover, sustained activation of podocyte NMDA receptors induces Ca(2+) influx, oxidative stress, loss of slit diaphragm proteins, and apoptosis. We observed that NMDA receptor subunits and their transcripts are increased in podocytes and mesangial cells cultured in elevated glucose compared with controls. A similar increase in NMDA subunits, especially NR1, NR2A, and NR2C, was observed in glomeruli and tubules of Akita mice...
October 2016: Diabetes
https://www.readbyqxmd.com/read/27382987/increase-of-total-nephron-albumin-filtration-and-reabsorption-in-diabetic-nephropathy
#14
Keita P Mori, Hideki Yokoi, Masato Kasahara, Hirotaka Imamaki, Akira Ishii, Takashige Kuwabara, Kenichi Koga, Yukiko Kato, Naohiro Toda, Shoko Ohno, Koichiro Kuwahara, Tomomi Endo, Kazuwa Nakao, Motoko Yanagita, Masashi Mukoyama, Kiyoshi Mori
The amount of albumin filtered through the glomeruli and reabsorbed at the proximal tubules in normal and in diabetic kidneys is debated. The megalin/cubilin complex mediates protein reabsorption, but genetic knockout of megalin is perinatally lethal. To overcome current technical problems, we generated a drug-inducible megalin-knockout mouse line, megalin(lox/lox);Ndrg1-CreER(T2) (iMegKO), in which megalin expression can be shut off at any time by administration of tamoxifen (Tam). Tam administration in adult iMegKO mice decreased the expression of renal megalin protein by 92% compared with that in wild-type C57BL/6J mice and almost completely abrogated renal reabsorption of intravenously injected retinol-binding protein...
July 6, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27367912/cannabinoid-receptors-in-the-kidney
#15
Deanne H Hryciw, Andrew J McAinch
PURPOSE OF REVIEW: The endocannabinoid system modulates cell signaling targets that are essential for energy homeostasis. Endocannabinoids bind to G protein-coupled receptors in the central nervous system and periphery, including the kidney. Modulation of cannabinoid receptor 1 (CB1) and CB2 activity in the kidney in diabetes and obesity has been identified as potential therapeutic target to reduce albuminuria and renal fibrosis. This review will highlight the results of recent studies that have identified a role for CB1 and CB2 in normal and pathological renal conditions...
September 2016: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/27355131/danshen-injection-ameliorates-stz-induced-diabetic-nephropathy-in-association-with-suppression-of-oxidative-stress-pro-inflammatory-factors-and-fibrosis
#16
Linhao Xu, Peiqiang Shen, Yanli Bi, Jian Chen, Zhangang Xiao, Xiaoming Zhang, Zheng Wang
Diabetic nephropathy (DN) is one of the most frequent complications in diabetes mellitus. This study aimed to explore whether Danshen injection is protective to renal tissue in diabetes. Intraperitoneal injection of streptozotocin (STZ) (60mg/kg) was used to induce diabetes in rats. Some STZ-induced diabetic rats were also intraperitoneally injected with Danshen solution at two different dosages (0.5 or 1ml/kg/day) for 6weeks. Our results showed that serum creatinine (sCr) and blood urea nitrogen were significantly increased in STZ-induced diabetic rats, which was alleviated upon Danshen injection...
September 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27247938/selective-insulin-resistance-in-the-kidney
#17
REVIEW
Shoko Horita, Motonobu Nakamura, Masashi Suzuki, Nobuhiko Satoh, Atsushi Suzuki, George Seki
Insulin resistance has been characterized as attenuation of insulin sensitivity at target organs and tissues, such as muscle and fat tissues and the liver. The insulin signaling cascade is divided into major pathways such as the PI3K/Akt pathway and the MAPK/MEK pathway. In insulin resistance, however, these pathways are not equally impaired. For example, in the liver, inhibition of gluconeogenesis by the insulin receptor substrate (IRS) 2 pathway is impaired, while lipogenesis by the IRS1 pathway is preserved, thus causing hyperglycemia and hyperlipidemia...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27226136/once-daily-administration-of-the-sglt2-inhibitor-empagliflozin-attenuates-markers-of-renal-fibrosis-without-improving-albuminuria-in-diabetic-db-db-mice
#18
Linda A Gallo, Micheal S Ward, Amelia K Fotheringham, Aowen Zhuang, Danielle J Borg, Nicole B Flemming, Ben M Harvie, Toni L Kinneally, Shang-Ming Yeh, Domenica A McCarthy, Hermann Koepsell, Volker Vallon, Carol Pollock, Usha Panchapakesan, Josephine M Forbes
Blood glucose control is the primary strategy to prevent complications in diabetes. At the onset of kidney disease, therapies that inhibit components of the renin angiotensin system (RAS) are also indicated, but these approaches are not wholly effective. Here, we show that once daily administration of the novel glucose lowering agent, empagliflozin, an SGLT2 inhibitor which targets the kidney to block glucose reabsorption, has the potential to improve kidney disease in type 2 diabetes. In male db/db mice, a 10-week treatment with empagliflozin attenuated the diabetes-induced upregulation of profibrotic gene markers, fibronectin and transforming-growth-factor-beta...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27164183/experimental-type-ii-diabetes-and-related-models-of-impaired-glucose-metabolism-differentially-regulate-glucose-transporters-at-the-proximal-tubule-brush-border-membrane
#19
Havovi Chichger, Mark E Cleasby, Surjit K Srai, Robert J Unwin, Edward S Debnam, Joanne Marks
What is the central question of this study? Although SGLT2 inhibitors represent a promising treatment for patients suffering from diabetic nephropathy, the influence of metabolic disruption on the expression and function of glucose transporters is largely unknown. What is the main finding and its importance? In vivo models of metabolic disruption (Goto-Kakizaki type II diabetic rat and junk-food diet) demonstrate increased expression of SGLT1, SGLT2 and GLUT2 in the proximal tubule brush border. In the type II diabetic model, this is accompanied by increased SGLT- and GLUT-mediated glucose uptake...
June 1, 2016: Experimental Physiology
https://www.readbyqxmd.com/read/27119088/combined-microencapsulated-islet-transplantation-and-revascularization-of-aortorenal-bypass-in-a-diabetic-nephropathy-rat-model
#20
Yunqiang He, Ziqiang Xu, Hongxing Fu, Bin Chen, Silu Wang, Bicheng Chen, Mengtao Zhou, Yong Cai
Objective. Revascularization of aortorenal bypass is a preferred technique for renal artery stenosis (RAS) in diabetic nephropathy (DN) patients. Restenosis of graft vessels also should be considered in patients lacking good control of blood glucose. In this study, we explored a combined strategy to prevent the recurrence of RAS in the DN rat model. Methods. A model of DN was established by intraperitoneal injection of streptozotocin. Rats were divided into 4 groups: SR group, MIT group, Com group, and the untreated group...
2016: Journal of Diabetes Research
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