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Mechanisms renal damage diabetes

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https://www.readbyqxmd.com/read/27873229/subclinical-kidney-damage-in-hypertensive-patients-a-renal-window-opened-on-the-cardiovascular-system-focus-on-microalbuminuria
#1
Giuseppe Mulè, Antonella Castiglia, Claudia Cusumano, Emilia Scaduto, Giulio Geraci, Dario Altieri, Epifanio Di Natale, Onofrio Cacciatore, Giovanni Cerasola, Santina Cottone
The kidney is one of the major target organs of hypertension.Kidney damage represents a frequent event in the course of hypertension and arterial hypertension is one of the leading causes of end-stage renal disease (ESRD).ESRD has long been recognized as a strong predictor of cardiovascular (CV) morbidity and mortality. However, over the past 20 years a large and consistent body of evidence has been produced suggesting that CV risk progressively increases as the estimated glomerular filtration rate (eGFR) declines and is already significantly elevated even in the earliest stages of renal damage...
November 22, 2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27830089/proteasome-activators-pa28%C3%AE-and-pa28%C3%AE-govern-development-of-microvascular-injury-in-diabetic-nephropathy-and-retinopathy
#2
Saeed Yadranji Aghdam, Ali Mahmoudpour
Diabetic nephropathy (DN) and diabetic retinopathy (DR) are major complications of type 1 and type 2 diabetes. DN and DR are mainly caused by injury to the perivascular supporting cells, the mesangial cells within the glomerulus, and the pericytes in the retina. The genes and molecular mechanisms predisposing retinal and glomerular pericytes to diabetic injury are poorly characterized. In this study, the genetic deletion of proteasome activator genes, PA28α and PA28β genes, protected the diabetic mice in the experimental STZ-induced diabetes model against renal injury and retinal microvascular injury and prolonged their survival compared with wild type STZ diabetic mice...
2016: International Journal of Nephrology
https://www.readbyqxmd.com/read/27777900/circulating-angiogenic-factors-in-diabetes-patients-in-a-tertiary-hospital-in-ghana
#3
Kwame Yeboah, Eric Kyei-Baafour, Daniel A Antwi, Henry Asare-Anane, Ben Gyan, Albert G B Amoah
BACKGROUND: Impaired angiogenesis is amongst the underlining mechanisms of organ damage in diabetes and hypertensive patients. In diabetes and hypertensive patients without proteinuria and overt CVDs, we studied the levels of angiogenic growth factors, angiopoietin (Ang)-1, Ang-2 and vascular endothelial growth factor (VEGF), and the relationship between these angiogenic growth factors and renal function, measured as estimated glomerular filtration rate (eGFR). METHOD: In a case control design, 107 type 2 diabetes (T2DM) patients and 93 non-diabetes controls were recruited into the study...
2016: Journal of Diabetes and Metabolic Disorders
https://www.readbyqxmd.com/read/27775793/microrna-125b-contributes-to-high-glucose-induced-reactive-oxygen-species-generation-and-apoptosis-in-hk-2-renal-tubular-epithelial-cells-by-targeting-angiotensin-converting-enzyme-2
#4
Y-F Huang, Y Zhang, C-X Liu, J Huang, G-H Ding
OBJECTIVE: Hyperglycemia induces apoptosis of renal tubular epithelial cells and contributes to tubular injury in diabetic nephropathy. Angiotensin-converting enzyme 2 (ACE2) is known to protect against diabetic kidney injury. However, the mechanism for the dysregulation of ACE2 expression in diabetic nephropathy is unclear. MATERIALS AND METHODS: Bioinformatic analysis and luciferase reporter assay were done to identify ACE2-targeting microRNAs. Gain- and loss-of-function experiments were performed to determine the biological roles of the ACE2-targeting microRNAs in high glucose-induced damage to renal tubular epithelial cells...
October 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27771702/role-of-the-renal-microcirculation-in-progression-of-chronic-kidney-injury-in-obesity
#5
Alejandro R Chade, John E Hall
Obesity is largely responsible for the growing incidence and prevalence of diabetes, cardiovascular and renal diseases. Current strategies to prevent and treat obesity and its consequences have been insufficient to reverse the ongoing trends. Lifestyle modification or pharmacological therapies often produce modest weight loss which is not sustained and recurrence of obesity is frequently observed, leading to progression of target organ damage in many obese subjects. Therefore, research efforts have focused not only on the factors that regulate energy balance, but also on understanding mechanisms of target organ injury in obesity...
2016: American Journal of Nephrology
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
#6
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/27754085/os-19-08-the-activated-intrarenal-renin-angiotensin-systems-and-oxidative-stress-in-tubular-can-be-the-original-mechanism-of-renal-damage-in-primary-aldosteronism
#7
Yoshitsugu Iwakura, Ryo Morimoto, Kumi Kikuchi, Yoshikiyo Ono, Yuta Tezuka, Yasuko Tsukada, Masahiro Nezu, Yasuhiro Igarashi, Masataka Kudo, Akira Nishiyama, Sadayoshi Ito, Fumitoshi Satoh
OBJECTIVE: High prevalence of renal damage has been demonstrated in patients with primary aldosteronism (PA). However, the original mechanism and onset still be elucidated. The purpose of this study is to investigate the possible original mechanisms of renal damages in PA. DESIGN AND METHOD: Consecutive 72 patients with aldosterone producing adenoma (APA) and 70 patients with essential hypertension (EH) participated. No patients had renal damages defined as eGFR (based on Cystatin C) < 60 ml/min/1...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27710853/hyperglycemia-induced-damage-to-mitochondrial-respiration-in-renal-mesangial-and-tubular-cells-implications-for-diabetic-nephropathy
#8
Anna Czajka, Afshan N Malik
Damage to renal tubular and mesangial cells is central to the development of diabetic nephropathy (DN), a complication of diabetes which can lead to renal failure. Mitochondria are the site of cellular respiration and produce energy in the form of ATP via oxidative phosphorylation, and mitochondrial dysfunction has been implicated in DN. Since the kidney is an organ with high bioenergetic needs, we postulated that hyperglycemia causes damage to renal mitochondria resulting in bioenergetic deficit. The bioenergetic profiles and the effect of hyperglycemia on cellular respiration of human primary mesangial (HMCs) and proximal tubular cells (HK-2) were compared in normoglycemic and hyperglycemic conditions using the seahorse bio-analyzer...
September 17, 2016: Redox Biology
https://www.readbyqxmd.com/read/27698952/epigallocatechin-3-gallate-attenuates-renal-damage-by-suppressing-oxidative-stress-in-diabetic-db-db-mice
#9
Xiu Hong Yang, Yu Pan, Xiao Li Zhan, Bao Long Zhang, Li Li Guo, Hui Min Jin
Epigallocatechin-3-gallate (EGCG), extracted from green tea, has been shown to have antioxidative activity. In the present study, we evaluated the effect of EGCG on the kidney function in db/db mice and also tried to investigate the underlying mechanism of the renoprotective effects of EGCG in both animals and cells. EGCG treatment could decrease the level of urinary protein, 8-iso-PGF2a, and Ang II. Moreover, EGCG could also change the level of several parameters associated with oxidative stress. In addition, the protein expression levels of AT-1R, p22-phox, p47-phox, p-ERK1/2, p-p38 MAPK, TGF-β1, and α-SMA in diabetic db/db mice were upregulated, and all of these symptoms were downregulated with the treatment of EGCG at 50 and 100 mg/kg/d...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27696667/the-anti-ageing-hormone-klotho-induces-nrf2-mediated-antioxidant-defences-in-human-aortic-smooth-muscle-cells
#10
Giuseppe Maltese, Paraskevi-Maria Psefteli, Benedetta Rizzo, Salil Srivastava, Luigi Gnudi, Giovanni E Mann, Richard C M Siow
Vascular ageing in conditions such as atherosclerosis, diabetes and chronic kidney disease, is associated with the activation of the renin angiotensin system (RAS) and diminished expression of antioxidant defences mediated by the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). The anti-ageing hormone klotho promotes longevity and protects against cardiovascular and renal diseases. Klotho has been shown to activate Nrf2 and attenuate oxidative damage in neuronal cells, however, the mechanisms by which it protects against vascular smooth muscle cell VSMC dysfunction elicited by Angiotensin II (AngII) remain to be elucidated...
October 3, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27692562/rhein-reverses-klotho-repression-via-promoter-demethylation-and-protects-against-kidney-and-bone-injuries-in-mice-with-chronic-kidney-disease
#11
Qin Zhang, Lin Liu, Wenjun Lin, Shasha Yin, Aiping Duan, Zhihong Liu, Wangsen Cao
Rhein is an anthraquinone compound isolated from the medicinal plant rhubarb and mainly used in the clinical treatment of diabetic nephropathy. Rhein exhibits various renoprotective functions, but the underlying mechanisms are not fully determined. However, its renoprotective properties recapitulate the role of Klotho, a renal-specific antiaging protein critical for maintaining kidney homeostasis. Here we explored the connections between rhein renoprotection and Klotho in a mouse model of adenine-induced chronic kidney disease...
September 27, 2016: Kidney International
https://www.readbyqxmd.com/read/27683034/intraglomerular-crosstalk-elaborately-regulates-podocyte-injury-and-repair-in-diabetic-patients-insights-from-a-3d-multiscale-modeling-study
#12
Hua Tan, Hualin Yi, Weiling Zhao, Jian-Xing Ma, Yuanyuan Zhang, Xiaobo Zhou
Podocytes are mainly involved in the regulation of glomerular filtration rate (GFR) under physiological condition. Podocyte depletion is a crucial pathological alteration in diabetic nephropathy (DN) and results in a broad spectrum of clinical syndromes such as protein urine and renal insufficiency. Recent studies indicate that depleted podocytes can be regenerated via differentiation of the parietal epithelial cells (PECs), which serve as the local progenitors of podocytes. However, the podocyte regeneration process is regulated by a complicated mechanism of cell-cell interactions and cytokine stimulations, which has been studied in a piecemeal manner rather than systematically...
September 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27664441/terpene-glycoside-component-from-moutan-cortex-ameliorates-diabetic-nephropathy-by-regulating-endoplasmic-reticulum-stress-related-inflammatory-responses
#13
Juan Chen, Xue-Feng Hou, Gang Wang, Qing-Xiang Zhong, Ying Liu, Hui-Hui Qiu, Nan Yang, Jun-Fei Gu, Chun-Fei Wang, Li Zhang, Jie Song, Lu-Qi Huang, Xiao-Bin Jia, Ming-Hua Zhang, Liang Feng
ETHNOPHARMACOLOGICAL RELEVANCE: Multiple lines of evidences have suggested that endoplasmic reticulum (ER) stress-related inflammatory responses play a critical role in the pathogenesis of diabetic nephropathy (DN). Moutan Cortex (MC), the root bark of Paeonia suffruticosa Andr., is a well-known traditional Chinese medicine (TCM), which has been used clinically for treating inflammatory diseases in China. The findings from our previous research suggested that terpene glycoside (TG) component of MC possessed favorable anti-inflammatory properties in curing DN...
September 21, 2016: Journal of Ethnopharmacology
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
#14
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/27643010/os-19-08-the-activated-intrarenal-renin-angiotensin-systems-and-oxidative-stress-in-tubular-can-be-the-original-mechanism-of-renal-damage-in-primary-aldosteronism
#15
Yoshitsugu Iwakura, Ryo Morimoto, Kumi Kikuchi, Yoshikiyo Ono, Yuta Tezuka, Yasuko Tsukada, Masahiro Nezu, Yasuhiro Igarashi, Masataka Kudo, Akira Nishiyama, Sadayoshi Ito, Fumitoshi Satoh
OBJECTIVE: High prevalence of renal damage has been demonstrated in patients with primary aldosteronism (PA). However, the original mechanism and onset still be elucidated. The purpose of this study is to investigate the possible original mechanisms of renal damages in PA. DESIGN AND METHOD: Consecutive 72 patients with aldosterone producing adenoma (APA) and 70 patients with essential hypertension (EH) participated. No patients had renal damages defined as eGFR (based on Cystatin C) < 60 ml/min/1...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27642745/-posttransplantation-diabetes-mellitus-in-patients-after-kidney-transplantation-incidence-and-risk-factors
#16
Isabell Jahn, Martin Busch, Undine Ott, Gunter Wolf, Wilgard Battefeld
BACKGROUND: Transplantation (NTX) associated ischemia-reperfusion-mechanisms and the predisposition for insulin resistance are discussed as causes of a posttransplantation diabetes mellitus (PTDM). Furthermore, immunosuppressants can have a damaging effect on insulin secretion. METHODS: 55 metabolically healthy patients with an endstage renal disease (age 52 ± 14 years, body mass index 27 ± 5 kg / m(2), blood pressure 137 ± 15/82 ± 11 mmHg) were included in a prospectively cohort study...
September 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27621182/regulation-of-the-ku70-and-apoptosis-related-proteins-in-experimental-diabetic-nephropathy
#17
Matem Tunçdemir, Melek Öztürk
BACKGROUND: Apoptosis contributes nephropathy pathogenesis in diabetes. However, its mechanisms still remain unclear. We examined the extent to which the angiotensin-II type 1 receptor blocker (AT1RB) irbesartan and the angiotensin converting enzyme inhibitor (ACEI) perindopril affected the apoptosis-related proteins Bcl-2, Bax, caspase-3, cytochrome-c and Ku70 in streptozotocin (STZ)-diabetic rats. MATERIALS AND METHODS: Animals were divided into five groups of eight each, four of which received STZ (60mg/kg in a single dose, i...
October 2016: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/27612496/differential-renal-effects-of-candesartan-at-high-and-ultra-high-doses-in-diabetic-mice-potential-role-of%C3%A2-ace2-at2r-mas
#18
Glaucia Callera, Tayze Antunes, Jose Correa, Danielle Moorman, Alexey Gutsol, Ying He, Aurelie Nguyen Dinh Cat, Ana M Briones, Augusto C Montezano, Kevin Burns, Rhian M Touyz
High doses of AngII receptor (AT1R) blockers (ARBs) are reno-protective in diabetes. Underlying mechanisms remain unclear. We evaluated whether high/ultra-high doses of candesartan (ARB) upregulate ACE2/Ang II type 2 receptor (AT2R)/Mas receptor (protective axis of the of the renin-angiotensin-system (RAS)) in diabetic mice. Systolic blood pressure (SBP), albuminuria, and expression/activity of RAS components were assessed in diabetic db/db and control db/+mice treated with increasing candesartan doses (intermediate, 1 mg/Kg/d; high, 5 mg/Kg/d; ultra-high, 25 and 75 mg/Kg/d; 4 weeks)...
September 9, 2016: Bioscience Reports
https://www.readbyqxmd.com/read/27611085/novel-protective-mechanism-of-reducing-renal-cell-damage-in-diabetes-activation-ampk-by-aicar-increased-nrf2-ogg1-proteins-and-reduced-oxidative-dna-damage
#19
Samy L Habib, Anamika Yadav, Dawit Kidane, Robert H Weiss, Sitai Liang
Exposure of renal cells to high glucose (HG) during diabetes has been recently proposed to be involved in renal injury. In the present study, we investigated a potential mechanism by which AICAR treatment regulates the DNA repair enzyme, 8-oxoG-DNA glycosylase (OGG1) in renal proximal tubular mouse cells exposed to HG and in kidney of db/db mice. Cells treated with HG for 2 days show inhibition in OGG1 promoter activity as well as OGG1 and Nrf2 protein expression. In addition, activation of AMPK by AICAR resulted in an increase raptor phosphorylation at Ser(792) and leads to increase the promoter activity of OGG1 through upregulation of Nrf2...
September 9, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27558173/development-of-a-functional-glomerulus-at-the-organ-level-on-a-chip-to-mimic-hypertensive-nephropathy
#20
Mengying Zhou, Xulang Zhang, Xinyu Wen, Taihua Wu, Weidong Wang, Mingzhou Yang, Jing Wang, Ming Fang, Bingcheng Lin, Hongli Lin
Glomerular hypertension is an important factor exacerbating glomerular diseases to end-stage renal diseases because, ultimately, it results in glomerular sclerosis (especially in hypertensive and diabetic nephropathy). The precise mechanism of glomerular sclerosis caused by glomerular hypertension is unclear, due partly to the absence of suitable in vitro or in vivo models capable of mimicking and regulating the complex mechanical forces and/or organ-level disease processes. We developed a "glomerulus-on-a-chip" (GC) microfluidic device...
2016: Scientific Reports
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