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Pathobiology of diabetes

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https://www.readbyqxmd.com/read/29325602/bile-acid-metabolism-in-liver-pathobiology
#1
John Y L Chiang, Jessica M Ferrell
Bile acids facilitate intestinal nutrient absorption and biliary cholesterol secretion to maintain bile acid homeostasis, which is essential for protecting liver and other tissues and cells from cholesterol and bile acid toxicity. Bile acid metabolism is tightly regulated by bile acid synthesis in the liver and bile acid biotransformation in the intestine. Bile acids are endogenous ligands that activate a complex network of nuclear receptor farnesoid X receptor and membrane G protein-coupled bile acid receptor-1 to regulate hepatic lipid and glucose metabolic homeostasis and energy metabolism...
January 11, 2018: Gene Expression
https://www.readbyqxmd.com/read/29259621/the-age-rage-axis-implications-for-age-associated-arterial-diseases
#2
REVIEW
Laura M Senatus, Ann Marie Schmidt
The process of advanced glycation leads to the generation and accumulation of an heterogeneous class of molecules called advanced glycation endproducts, or AGEs. AGEs are produced to accelerated degrees in disorders such as diabetes, renal failure, inflammation, neurodegeneration, and in aging. Further, AGEs are present in foods and in tobacco products. Hence, through both endogenous production and exogenous consumption, AGEs perturb vascular homeostasis by a number of means; in the first case, AGEs can cause cross-linking of long-lived molecules in the basement membranes such as collagens, thereby leading to "vascular stiffening" and processes that lead to hyperpermeability and loss of structural integrity...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/29228112/xenotransplantation-the-current-status-and-prospects
#3
D K C Cooper, R Gaston, D Eckhoff, J Ladowski, T Yamamoto, L Wang, H Iwase, H Hara, M Tector, A J Tector
Introduction: There is a continuing worldwide shortage of organs from deceased human donors for transplantation into patients with end-stage organ failure. Genetically engineered pigs could resolve this problem, and could also provide tissues and cells for the treatment of conditions such as diabetes, Parkinson's disease and corneal blindness. Sources of data: The current literature has been reviewed. Areas of agreement: The pathobiologic barriers are now largely defined...
December 8, 2017: British Medical Bulletin
https://www.readbyqxmd.com/read/29149824/the-role-of-gene-therapy-in-the-treatment-of-retinal-diseases-a-review
#4
Claudio Campa, Carla Enrica Gallenga, Elena Bolletta, Paolo Perri
Background: Gene therapy represents the therapeutic delivery of nucleic acid polymers into a patient's cells with the aim of treating an underlying disease. Over the past 2 decades this new therapy has made substantial progress owing to better understanding of the pathobiologic basis of various diseases coupled with growth of gene transfer biotechnologies. The eye, in particular, represents a suitable target for such therapy due to the immune privilege provided by the blood-ocular barrier, the ability to directly visualize, access and locally treat the cells and the minimal amount of vector needed given the size of this organ...
November 16, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/28890305/relationships-between-blood-pressure-and-blood-glucose-among-offspring-of-parents-with-type-2-diabetes-prediction-of-incident-dysglycemia-in-a-biracial-cohort
#5
Chimaroke Edeoga, Ibiye Owei, Krishmita Siwakoti, Nkiru Umekwe, Fatoumatta Ceesay, Jim Wan, Sam Dagogo-Jack
AIMS: We assessed blood pressure (BP) and blood glucose (BG) values in healthy subjects, and examined baseline BP as a predictor of incident prediabetes during follow-up. METHODS: Participants in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study underwent screening assessments (anthropometry, BP, OGTT) and were stratified into normal BP (NBP), prehypertension, or hypertension, and normal glucose regulation (NGR), prediabetes (IFG/IGT), or type 2 diabetes (T2D) status...
August 2, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28839322/breast-cancer-in-a-patient-with-kindlers-syndrome
#6
Itrat Mehdi, Bassim Jaffar Al Bahrani, Taha Mohsin Al Lawati, Zahid Al Mandhari, Fatima Ramadhan Al Lawati
Breast Cancer (BC) has associated risk factors and genetic factors like BRCA1, and BRCA2. Many benign and malignant disease processes are found concurrently with BC and believed to be additional risk factors like gall bladder stones (cholelithiasis), hypertension, diabetes mellitus, cerebrovascular lesions, arthritis, spine and spinal cord degenerative lesions, infertility, depression, sleep disturbances, obesity, autoimmune diseases (SLE), and thyroid diseases. There are some malignant disease associations like synchronous or metachronous ovarian, colonic and endometrial tumours with Breast cancer...
August 2017: JPMA. the Journal of the Pakistan Medical Association
https://www.readbyqxmd.com/read/28739642/animal-models-of-ocular-angiogenesis-from-development-to-pathologies
#7
REVIEW
Chi-Hsiu Liu, Zhongxiao Wang, Ye Sun, Jing Chen
Pathological angiogenesis in the eye is an important feature in the pathophysiology of many vision-threatening diseases, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration, as well as corneal diseases with abnormal angiogenesis. Development of reproducible and reliable animal models of ocular angiogenesis has advanced our understanding of both the normal development and the pathobiology of ocular neovascularization. These models have also proven to be valuable experimental tools with which to easily evaluate potential antiangiogenic therapies beyond eye research...
July 24, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28659725/system-level-meta-analysis-of-microarray-datasets-for-elucidation-of-diabetes-mellitus-pathobiology
#8
Aditya Saxena, Kumar Sachin, Ashok Kumar Bhatia
BACKGROUND: Type 2 diabetes (T2D) is a common multi-factorial disease that is primarily ac-counted to ineffective insulin action in lowering blood glucose level and later escalates to impaired insu-lin secretion by pancreatic β cells. Deregulation in insulin signaling to its target organs is attributed to this disease phenotype. Various genome-wide microarray studies from multiple insulin responsive tis-sues have been conducted in past but due to inherent noise in microarray data and heterogeneity in dis-ease etiology; reproduction of prioritized pathways/genes is very low across various studies...
June 2017: Current Genomics
https://www.readbyqxmd.com/read/28585212/lipotoxicity-related-hematological-disorders-in-obesity
#9
REVIEW
Ibrahim Celalettin Haznedaroglu, Umit Yavuz Malkan
Lipotoxicity can mediate endothelial dysfunction in obesity. Altered endothelial cell phenotype during the pathobiological course of the lipotoxicity may lead to the hemostatic abnormalities, which is a hallmark of several hematological disorders. Impaired hemostasis could also be directly related to the numerous metabolic diseases such as hypertension, diabetes and atherosclerosis. On the other hand, local hematopoietic bone marrow (BM) renin-angiotensin system (RAS) contributes to the development of atherosclerosis via acting on the lipotoxicity processes...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28385385/deactivating-fatty-acids-acyl-coa-thioesterase-mediated-control-of-lipid-metabolism
#10
REVIEW
Veronika Tillander, Stefan E H Alexson, David E Cohen
The cellular uptake of free fatty acids (FFA) is followed by esterification to coenzyme A (CoA), generating fatty acyl-CoAs that are substrates for oxidation or incorporation into complex lipids. Acyl-CoA thioesterases (ACOTs) constitute a family of enzymes that hydrolyze fatty acyl-CoAs to form FFA and CoA. Although biochemically and biophysically well characterized, the metabolic functions of these enzymes remain incompletely understood. Existing evidence suggests regulatory roles in controlling rates of peroxisomal and mitochondrial fatty acyl-CoA oxidation, as well as in the subcellular trafficking of fatty acids...
July 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28377846/a-quantitative-approach-to-predict-differential-effects-of-anti-vegf-treatment-on-diffuse-and-focal-leakage-in-patients-with-diabetic-macular-edema-a-pilot-study
#11
Michael J Allingham, Dibyendu Mukherjee, Erin B Lally, Hossein Rabbani, Priyatham S Mettu, Scott W Cousins, Sina Farsiu
PURPOSE: We use semiautomated segmentation of fluorescein angiography (FA) to determine whether anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular edema (DME) differentially affects microaneurysm (MA)-associated leakage, termed focal leakage, versus non-MA-associated leakage, termed diffuse leakage. METHODS: We performed a retrospective study of 29 subjects treated with at least three consecutive injections of anti-VEGF agents for DME (mean 4...
March 2017: Translational Vision Science & Technology
https://www.readbyqxmd.com/read/28210739/retinal-oxidative-stress-at-the-onset-of-diabetes-determined-by-synchrotron-ftir-widefield-imaging-towards-diabetes-pathogenesis
#12
Ebrahim Aboualizadeh, Mahsa Ranji, Christine M Sorenson, Reyhaneh Sepehr, Nader Sheibani, Carol J Hirschmugl
Diabetic retinopathy is a microvascular complication of diabetes that can lead to blindness. In the present study, we aimed to determine the nature of diabetes-induced, highly localized biochemical changes in the neuroretina at the onset of diabetes. High-resolution synchrotron Fourier transform infrared (s-FTIR) wide field microscopy coupled with multivariate analysis (PCA-LDA) was employed to identify biomarkers of diabetic retinopathy with spatial resolution at the cellular level. We compared the retinal tissue prepared from 6-week-old Ins2(Akita/+) heterozygous (Akita/+, N = 6; a model of diabetes) male mice with the wild-type (control, N = 6) mice...
March 27, 2017: Analyst
https://www.readbyqxmd.com/read/28209006/a-comparative-evaluation-of-serum-magnesium-in-diabetes-mellitus-type-2-patients-with-and-without-periodontitis-a-clinico-biochemical-study
#13
Akshatha Shetty, Rahul Bhandary, Biju Thomas, Amitha Ramesh
INTRODUCTION: Magnesium is an essential cation playing a crucial role in many physiological functions and its imbalance is associated with greater number of pathological situations. Oxidative stress is usually increased due to decreased essential nutrients. Hence, any imbalance of essential nutrients like serum magnesium can significantly play a role in the pathobiology of periodontitis in the presence of diabetes, as diabetes and chronic periodontitis are two chronic diseases that have been biologically linked...
December 2016: Journal of Clinical and Diagnostic Research: JCDR
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
#14
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...
April 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28062508/arterial-calcification-in-diabetes-mellitus-preclinical-models-and-translational-implications
#15
REVIEW
John N Stabley, Dwight A Towler
Diabetes mellitus increasingly afflicts our aging and dysmetabolic population. Type 2 diabetes mellitus and the antecedent metabolic syndrome represent the vast majority of the disease burden-increasingly prevalent in children and older adults. However, type 1 diabetes mellitus is also advancing in preadolescent children. As such, a crushing wave of cardiometabolic disease burden now faces our society. Arteriosclerotic calcification is increased in metabolic syndrome, type 2 diabetes mellitus, and type 1 diabetes mellitus-impairing conduit vessel compliance and function, thereby increasing the risk for dementia, stroke, heart attack, limb ischemia, renal insufficiency, and lower extremity amputation...
February 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28004036/the-microbial-hypothesis-contributions-of-adenovirus-infection-and-metabolic-endotoxaemia-to-the-pathogenesis-of-obesity
#16
REVIEW
Amos Tambo, Mohsin H K Roshan, Nikolai P Pace
The global obesity epidemic, dubbed "globesity" by the World Health Organisation, is a pressing public health issue. The aetiology of obesity is multifactorial incorporating both genetic and environmental factors. Recently, epidemiological studies have observed an association between microbes and obesity. Obesity-promoting microbiome and resultant gut barrier disintegration have been implicated as key factors facilitating metabolic endotoxaemia. This is an influx of bacterial endotoxins into the systemic circulation, believed to underpin obesity pathogenesis...
2016: International Journal of Chronic Diseases
https://www.readbyqxmd.com/read/27916653/pericytes-an-overlooked-player-in-vascular-pathobiology
#17
REVIEW
David Ferland-McCollough, Sadie Slater, Jai Richard, Carlotta Reni, Giuseppe Mangialardi
Pericytes are a heterogeneous population of cells located in the blood vessel wall. They were first identified in the 19th century by Rouget, however their biological role and potential for drug targeting have taken time to be recognised. Isolation of pericytes from several different tissues has allowed a better phenotypic and functional characterization. These findings revealed a tissue-specific, multi-functional group of cells with multilineage potential. Given this emerging evidence, pericytes have acquired specific roles in pathobiological events in vascular diseases...
March 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27855634/identification-of-novel-targets-of-diabetic-nephropathy-and-pedf-peptide-treatment-using-rna-seq
#18
Ana Rubin, Anna C Salzberg, Yuka Imamura, Anzor Grivitishvilli, Joyce Tombran-Tink
BACKGROUND: Diabetic nephropathy (DN) is a major complication of type1 and type 2 diabetes. Understanding how diabetes regulate transcriptome dynamics in DN is important for understanding the biology of the disease and for guiding development of new treatments. RESULTS: We analyzed the kidney transcriptome of a DN mouse model, D2.B6-Ins2 (Akita) /MatbJ, before/after treatment with P78-PEDF. Age, weight, and gender-matched mice and wild-type (wt) littermates were treated at 6 weeks (early treatment) or 12 weeks (late treatment) of age for the duration of 6 weeks...
November 17, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27760067/role-of-asymmetrical-dimethylarginine-in-diabetic-microvascular-complications
#19
Mei-Rong Du, Gui-Xia Ju, Nian-Sheng Li, Jun-Lin Jiang
Microvascular complications are the leading causes of acquired blindness, end-stage renal failure, and varieties of neuropathy associated with diabetes. Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, is involved in endothelial dysfunction, oxidative stress, and inflammation associated with the progression of diabetic microvascular complications. Elevated ADMA has been detected in experimental animals and patients with diabetic microangiopathy like retinopathy, nephropathy, and neuropathy...
October 2016: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/27703986/the-yin-and-yang-of-the-opioid-growth-regulatory-system-focus-on-diabetes-the-lorenz-e-zimmerman-tribute-lecture
#20
REVIEW
Joseph W Sassani, Patricia J Mc Laughlin, Ian S Zagon
The Opioid Growth Regulatory System consists of opioid growth factor (OGF), [Met(5)]-enkephalin, and its unique receptor (OGFr). OGF inhibits cell division when bound to OGFr. Conversely, blockade of the interaction of OGF and OGFr, using the potent, long-acting opioid receptor antagonist, naltrexone (NTX), results in increased DNA synthesis and cell division. The authors have demonstrated both in vitro and in vivo that the addition of exogenous OGF or an increase in available OGFr decreases corneal epithelial cell division and wound healing...
2016: Journal of Diabetes Research
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