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Pathophysiology diabetic injury

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https://www.readbyqxmd.com/read/29580581/acute-kidney-injury-and-progression-of-diabetic-kidney-disease
#1
REVIEW
Samuel Mon-Wei Yu, Joseph V Bonventre
Diabetic kidney disease, commonly termed diabetic nephropathy (DN), is the most common cause of end-stage kidney disease (ESKD) worldwide. The characteristic histopathology of DN includes glomerular basement membrane thickening, mesangial expansion, nodular glomerular sclerosis, and tubulointerstitial fibrosis. Diabetes is associated with a number of metabolic derangements, such as reactive oxygen species overproduction, hypoxic state, mitochondrial dysfunction, and inflammation. In the past few decades, our knowledge of DN has advanced considerably although much needs to be learned...
March 2018: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/29574759/humanizing-the-mouse-immune-system-to-study-splanchnic-organ-inflammation
#2
Brianyell McDaniel, Matthew B Grisham
It is well known that alterations in splanchnic organ perfusion and/or immune regulation may produce inflammatory tissue injury similar to that observed in several human disorders such as ischemia and reperfusion injury, food allergies, diabetes, inflammatory bowel disease and graft-versus-host disease. Mouse models have been tremendously important in defining the roles of the circulation, leukocyte trafficking, inflammatory mediator generation, immune regulation and the intestinal microbiota in the pathogenesis of acute and chronic inflammation...
March 24, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29527173/obesity-metabolic-syndrome-and-musculoskeletal-disease-common-inflammatory-pathways-suggest-a-central-role-for-loss-of-muscle-integrity
#3
REVIEW
Kelsey H Collins, Walter Herzog, Graham Z MacDonald, Raylene A Reimer, Jaqueline L Rios, Ian C Smith, Ronald F Zernicke, David A Hart
Inflammation can arise in response to a variety of stimuli, including infectious agents, tissue injury, autoimmune diseases, and obesity. Some of these responses are acute and resolve, while others become chronic and exert a sustained impact on the host, systemically, or locally. Obesity is now recognized as a chronic low-grade, systemic inflammatory state that predisposes to other chronic conditions including metabolic syndrome (MetS). Although obesity has received considerable attention regarding its pathophysiological link to chronic cardiovascular conditions and type 2 diabetes, the musculoskeletal (MSK) complications (i...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29523680/overcoming-translational-barriers-in-acute-kidney-injury-a-report-from-an-niddk-workshop
#4
Anna Zuk, Paul M Palevsky, Linda Fried, Frank E Harrell, Samina Khan, Dianne B McKay, Luke Devey, Lakhmir Chawla, Mark de Caestecker, James S Kaufman, B Taylor Thompson, Anupam Agarwal, Tom Greene, Mark Douglas Okusa, Joseph V Bonventre, Laura M Dember, Kathleen D Liu, Benjamin D Humphreys, Daniel Gossett, Yining Xie, Jenna M Norton, Paul L Kimmel, Robert A Star
AKI is a complex clinical condition associated with high mortality, morbidity, and health care costs. Despite improvements in methodology and design of clinical trials, and advances in understanding the underlying pathophysiology of rodent AKI, no pharmacologic agent exists for the prevention or treatment of AKI in humans. To address the barriers that affect successful clinical translation of drug targets identified and validated in preclinical animal models of AKI in this patient population, the National Institute of Diabetes and Digestive and Kidney Diseases convened the "AKI Outcomes: Overcoming Barriers in AKI" workshop on February 10-12, 2015...
March 9, 2018: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/29522878/quantification-of-molecular-heterogeneity-in-kidney-tissue-by-targeted-proteomics
#5
K Johanna R Hoyer, Sebastian Dittrich, Malte P Bartram, Markus M Rinschen
Renal diseases are driven by alterations in the entity of proteins within the kidney, at the level of single cells, nephron subunits (such as glomerulus and tubule), tissues and body fluids. Histologically, kidney diseases are extremely heterogeneous. Mass-spectrometry based proteomics provides a unique opportunity to interrogate heterogeneity and dynamics of various proteome layers within the kidney to better understand physiology and pathophysiology, and to translate signaling networks into therapies. Yet, the success of this endeavor will largely depend on improving proteomic data acquisition methods toward increased reproducibility...
March 6, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29520569/mathematical-model-for-glucose-dependence-of-the-local-renin-angiotensin-system-in-podocytes
#6
Minu R Pilvankar, Michele A Higgins, Ashlee N Ford Versypt
Diabetic kidney disease (DKD) is the primary cause of kidney failure. Diabetic hyperglycemia primarily damages podocyte cells. Podocytes express a local renin-angiotensin system (RAS) that produces angiotensin II (ANG II). ANG II levels are elevated by hyperglycemia, triggering podocyte injury. Quantitative descriptions of glucose dose dependency of ANG II are scarce in the literature. For better understanding of the mechanism of glycemic injury in DKD, a mathematical model is developed to describe the glucose-stimulated local RAS in podocytes...
March 8, 2018: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/29474750/suppressed-heat-shock-protein-response-in-the-kidney-of-exercise-trained-diabetic-rats
#7
J Lappalainen, N K J Oksala, D E Laaksonen, S Khanna, T Kokkola, K Kaarniranta, C K Sen, M Atalay
Impaired expression of heat shock proteins (HSPs) and increased oxidative stress may contribute to the pathophysiology of diabetes by disrupted tissue protection. Acute exercise induces oxidative stress, whereas exercise training up-regulates endogenous antioxidant defenses and HSP expression. Although diabetic nephropathy is a major contributor to diabetic morbidity, information regarding the effect of HSPs on kidney protection is limited. The present study evaluated the effects of 8-week exercise training on kidney HSP expression and markers of oxidative stress at rest and after acute exercise in rats with or without streptozotocin-induced diabetes...
February 23, 2018: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/29452961/dipeptidyl-peptidase-4-inhibitors-dpp-4i-combined-with-vitamin-d3-an-exploration-to-treat-new-onset-type-1-diabetes-mellitus-and-latent-autoimmune-diabetes-in-adults-in-the-future
#8
Marcelo Maia Pinheiro, Felipe Moura Maia Pinheiro, Maria Luisa Trabachin
Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by destruction of pancreatic beta cells through cell injury caused primarily by cytotoxic T lymphocytes (CD8 + ). The pathophysiological basis of T1DM seems to be an imbalance between a reduced function of T regulatory lymphocytes and an increased inflammatory activity of Th17 lymphocytes caused by increased production of inflammatory cytokines, as IL-1β, IL-6, IL-17 and IFN-gamma due to environmental factors and genetic predisposition...
February 13, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29442529/signaling-mediators-modulated-by-cardioprotective-interventions-in-healthy-and-diabetic-myocardium-with-ischaemia-reperfusion-injury
#9
Feyzizadeh Saeid, Javadi Aniseh, Badalzadeh Reza, Vafaee S Manouchehr
Ischaemic heart diseases are one of the major causes of death in the world. In most patients, ischaemic heart disease is coincident with other risk factors such as diabetes. Patients with diabetes are more prone to cardiac ischaemic dysfunctions including ischaemia-reperfusion injury. Ischaemic preconditioning, postconditioning and remote conditionings are reliable interventions to protect the myocardium against ischaemia-reperfusion injuries through activating various signaling pathways and intracellular mediators...
January 1, 2018: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/29399065/inhibition-of-mir-186-5p-contributes-to-high-glucose-induced-injury-in-ac16-cardiomyocytes
#10
Jiamei Jiang, Hailiang Mo, Chang Liu, Bin Wu, Zijun Wu, Xingyue Li, Teng Li, Songjian He, Shanghai Li, Qiong You, Keng Wu, Runmin Guo
A growing body of evidence has demonstrated that microRNAs (miRs) have pivotal roles in the pathophysiological development mechanisms of diabetic cardiomyopathy (DCM). Previous studies have demonstrated that miR-186-5p was significantly decreased in DCM. In addition, it has recently been reported that an imbalance of miR-186 is associated with a variety of physiological and pathological processes. Therefore, the present study was designed to investigate the role of miR-186-5p in high glucose (HG)-induced cytotoxicity and apoptosis in AC16 cardiomyocytes...
January 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29393089/renal-effects-of-hyperuricemia
#11
Carlos Enrique Méndez Landa
BACKGROUND: From a clinical point of view, uric acid has been dismissed as a cause of injury and renal progression, and the mechanisms by which uric acid directly causes renal injury have not been fully understood. Hyperuricemia is associated with metabolic syndrome, diabetes, hypertension, and kidney and cardiovascular diseases. Although it remains controversial whether hyperuricemia is a causal factor for kidney disease, kidneys play a major role in the regulation of serum uric acid levels...
2018: Contributions to Nephrology
https://www.readbyqxmd.com/read/29344670/pgc-1%C3%AE-ameliorates-kidney-fibrosis-in-mice-with-diabetic-kidney-disease-through-an-antioxidative-mechanism
#12
Liwen Zhang, Jian Liu, Fangfang Zhou, Weiming Wang, Nan Chen
The production of reactive oxygen species (ROS) is a common phenomenon in podocyte impairment, which leads to the irreversible progression of chronic kidney diseases, such as diabetic kidney disease (DKD). Previous research has indicated that peroxisome proliferator‑activated receptor γ (PPARγ) coactivator‑1α (PGC‑1α) participates in mitochondrial biogenesis and energy metabolism in certain mitochondria‑enriched cells, including myocardial and skeletal muscle cells. Therefore, we hypothesized that PGC‑1α may be a protective nuclear factor against energy and oxidative stress in DKD...
January 16, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29344292/galectin-3-activation-and-inhibition-in-heart-failure-and-cardiovascular-disease-an-update
#13
REVIEW
Navin Suthahar, Wouter C Meijers, Herman H W Silljé, Jennifer E Ho, Fu-Tong Liu, Rudolf A de Boer
Galectin-3 is a versatile protein orchestrating several physiological and pathophysiological processes in the human body. In the last decade, considerable interest in galectin-3 has emerged because of its potential role as a biotarget. Galectin-3 is differentially expressed depending on the tissue type, however its expression can be induced under conditions of tissue injury or stress. Galectin-3 overexpression and secretion is associated with several diseases and is extensively studied in the context of fibrosis, heart failure, atherosclerosis and diabetes mellitus...
2018: Theranostics
https://www.readbyqxmd.com/read/29340699/long-term-expression-of-glomerular-genes-in-diabetic-nephropathy
#14
Dominik Chittka, Bernhard Banas, Laura Lennartz, Franz Josef Putz, Kathrin Eidenschink, Sebastian Beck, Thomas Stempfl, Christoph Moehle, Simone Reichelt-Wurm, Miriam C Banas
Background: Although diabetic nephropathy (DN) is the most common cause for end-stage renal disease in western societies, its pathogenesis still remains largely unclear. A different gene pattern of diabetic and healthy kidney cells is one of the probable explanations. Numerous signalling pathways have emerged as important pathophysiological mechanisms for diabetes-induced renal injury. Methods: Glomerular cells, as podocytes or mesangial cells, are predominantly involved in the development of diabetic renal lesions...
January 11, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29332180/cd39-adenosinergic-axis-in-renal-pathophysiology-and-therapeutics
#15
REVIEW
Bellamkonda K Kishore, Simon C Robson, Karen M Dwyer
Extracellular ATP interacts with purinergic type 2 (P2) receptors and elicits many crucial biological functions. Extracellular ATP is sequentially hydrolyzed to ADP and AMP by the actions of defined nucleotidases, such as CD39, and AMP is converted to adenosine, largely by CD73, an ecto-5'-nucleotidase. Extracellular adenosine interacts with P1 receptors and often opposes the effects of P2 receptor activation. The balance between extracellular ATP and adenosine in the blood and extracellular fluid is regulated chiefly by the activities of CD39 and CD73, which constitute the CD39-adenosinergic axis...
January 13, 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29288897/increased-trpc6-expression-is-associated-with-tubular-epithelial-cell-proliferation-and-inflammation-in-diabetic-nephropathy
#16
Yanqin Fu, Chongxian Wang, Dongming Zhang, Yaping Xin, Jun Li, Yuanyuan Zhang, Xiaojing Chu
Although TRPC6 expression is shown to be significantly elevated in a rat model diabetic nephropathy (DN), its expression and role in human DN are unclear. We thus explored the role of TRPC6 in the pathophysiology of tubular epithelial cell injury following DN. HK-2 cells were cultured in a high-glucose medium to induce a DN cell model. Ad-TRPC6 and TRP6 siRNA were transfected to overexpress and knock down TRPC6. We found that TRPC6 expression was significantly upregulated in DN tissues and cells. TRPC6 siRNA inhibited cell proliferation and promoted cell apoptosis in HK-2 cells treated with high glucose, whereas Ad-TRPC6 showed the opposite effect...
February 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29279880/pathophysiology-of-the-underactive-bladder
#17
REVIEW
Naoki Aizawa, Yasuhiko Igawa
Underactive bladder (UAB), which has been described as a symptom complex suggestive of detrusor underactivity, is usually characterized by prolonged urination time with or without a sensation of incomplete bladder emptying, usually with hesitancy, reduced sensation on filling, and slow stream often with storage symptoms. Several causes such as aging, bladder outlet obstruction, diabetes mellitus, neurologic disorders, and nervous injury to the spinal cord, cauda equine, and peripheral pelvic nerve have been assumed to be responsible for the development of UAB...
December 2017: Investigative and Clinical Urology
https://www.readbyqxmd.com/read/29209776/hyperoxia-induced-cardiotoxicity-and-ventricular-remodeling-in-type-ii-diabetes-mice
#18
Jennifer Leigh Rodgers, Eva Samal, Subhra Mohapatra, Siva Kumar Panguluri
Hyperoxia, or supplemental oxygen, is regularly used in the clinical setting for critically ill patients in ICU. However, several recent studies have demonstrated the negative impact of this treatment in patients in critical care, including increased rates of lung and cardiac injury, as well as increased mortality. The purpose of this study was to determine the predisposition for arrhythmias and electrical remodeling in a type 2 diabetic mouse model (db/db), as a result of hyperoxia treatment. For this, db/db and their heterozygous controls were treated with hyperoxia (> 90% oxygen) or normoxia (normal air) for 72-h...
December 5, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/29191563/tgf-%C3%AE-1-p53-signaling-in-renal-fibrogenesis
#19
REVIEW
Stephen P Higgins, Yi Tang, Craig E Higgins, Badar Mian, Wenzheng Zhang, Ralf-Peter Czekay, Rohan Samarakoon, David J Conti, Paul J Higgins
Fibrotic disorders of the renal, pulmonary, cardiac, and hepatic systems are associated with significant morbidity and mortality. Effective therapies to prevent or curtail the advancement to organ failure, however, remain a major clinical challenge. Chronic kidney disease, in particular, constitutes an increasing medical burden affecting >15% of the US population. Regardless of etiology (diabetes, hypertension, ischemia, acute injury, urologic obstruction), persistently elevated TGF-β1 levels are causatively linked to the activation of profibrotic signaling networks and disease progression...
March 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29111542/a-call-to-action-to-develop-integrated-curricula-in-cardiorenal-medicine
#20
Claudio Ronco, Federico Ronco, Peter A McCullough
With the adoption of the new definition and classification of cardiorenal syndrome (CRS) and its relevant subtypes, much attention has been placed on elucidating the mechanisms of heart and kidney interactions. The pathophysiologic pathways are of great interest by which acute heart failure may result in acute kidney injury (AKI; type 1), chronic heart failure accelerates the progression of chronic kidney disease (CKD; type 2), AKI provokes cardiac events (type 3), and CKD increases the risk and severity of cardiovascular disease (type 4)...
2017: Reviews in Cardiovascular Medicine
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