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Pathobiology of diabetes

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https://www.readbyqxmd.com/read/28210739/retinal-oxidative-stress-at-the-onset-of-diabetes-determined-by-synchrotron-ftir-widefield-imaging-towards-diabetes-pathogenesis
#1
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...
February 17, 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
#2
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
#3
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...
February 13, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28062508/arterial-calcification-in-diabetes-mellitus-preclinical-models-and-translational-implications
#4
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...
December 22, 2016: 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
#5
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
#6
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...
December 1, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27855634/identification-of-novel-targets-of-diabetic-nephropathy-and-pedf-peptide-treatment-using-rna-seq
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/27544892/targeted-near-infrared-fluorescence-imaging-of%C3%A2-atherosclerosis-clinical-and-intracoronary-evaluation-of-indocyanine-green
#10
Johan W Verjans, Eric A Osborn, Giovanni J Ughi, Marcella A Calfon Press, Ehsan Hamidi, Antonios P Antoniadis, Michail I Papafaklis, Mark F Conrad, Peter Libby, Peter H Stone, Richard P Cambria, Guillermo J Tearney, Farouc A Jaffer
OBJECTIVES: This study sought to determine whether indocyanine green (ICG)-enhanced near-infrared fluorescence (NIRF) imaging can illuminate high-risk histologic plaque features of human carotid atherosclerosis, and in coronary atheroma of living swine, using intravascular NIRF-optical coherence tomography (OCT) imaging. BACKGROUND: New translatable imaging approaches are needed to identify high-risk biological signatures of atheroma. ICG is a U.S. Food and Drug Administration-approved NIRF imaging agent that experimentally targets plaque macrophages and lipid in areas of enhanced endothelial permeability...
September 2016: JACC. Cardiovascular Imaging
https://www.readbyqxmd.com/read/27455994/rethinking-nuclear-receptors-as-potential-therapeutic-targets-for-retinal-diseases
#11
REVIEW
Mayur Choudhary, Goldis Malek
Collectively, retinal diseases, including age-related macular degeneration, retinitis pigmentosa, and diabetic retinopathy, result in severe vision impairment worldwide. The absence and/or limited availability of successful drug therapies for these blinding disorders necessitates further understanding their pathobiology and identifying new targetable signaling pathways. Nuclear receptors are transcription regulators of many key aspects of human physiology, as well as pathophysiology, with reported roles in development, aging, and disease...
July 25, 2016: Journal of Biomolecular Screening
https://www.readbyqxmd.com/read/27430991/plasma-lipid-levels-predict-dysglycemia-in-a-biracial-cohort-of-nondiabetic-subjects-potential-mechanisms
#12
Ibiye Owei, Nkiru Umekwe, Jim Wan, Samuel Dagogo-Jack
Dyslipidemia and dysglycemia are etiologically associated, but the direction, chronology, and mechanisms of the association are not fully understood. We, therefore, analyzed data from 335 healthy adults (184 black, 151 white) enrolled in the Pathobiology of Prediabetes in A Biracial Cohort study. Subjects underwent oral glucose tolerance test (OGTT) and were enrolled if they had normal fasting and 2-h plasma glucose levels. Assessments during year 1 included anthropometry, fasting lipid profile, insulin sensitivity, and insulin secretion...
November 2016: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27326327/in-vitro-metabolic-stability-and-in-vivo-biodistribution-of-3-methyl-4-furoxancarbaldehyde-using-pet-imaging-in-rats
#13
Adam B Pippin, Zaira Hidayah Mohd Arshad, Ronald J Voll, Jonathon A Nye, Sussan Ghassabian, Craig M Williams, Alessandra Mancini, Dennis C Liotta, Maree T Smith, Mark M Goodman
Painful diabetic neuropathy (PDN) is a type of peripheral neuropathic pain that is currently difficult to treat using clinically available analgesics. Recent work suggests a progressive depletion of nitric oxide (NO) in nerve cells may be responsible for the pathobiology of PDN. The nitric oxide donor, 3-methyl-4-furoxancarbaldehyde (PRG150), has been shown to produce dose-dependent analgesia in a rat model of PDN. To gain insight into the mechanism of analgesia, methods to radiolabel PRG150 were developed to assess the in vivo biodistribution in rats...
June 9, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27313539/molecular-markers-of-diabetic-retinopathy-potential-screening-tool-of-the-future
#14
REVIEW
Priyia Pusparajah, Learn-Han Lee, Khalid Abdul Kadir
Diabetic retinopathy (DR) is among the leading causes of new onset blindness in adults. Effective treatment may delay the onset and progression of this disease provided it is diagnosed early. At present retinopathy can only be diagnosed via formal examination of the eye by a trained specialist, which limits the population that can be effectively screened. An easily accessible, reliable screening biomarker of diabetic retinopathy would be of tremendous benefit in detecting the population in need of further assessment and treatment...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27191267/identification-of-polycystic-ovary-syndrome-potential-drug-targets-based-on-pathobiological-similarity-in-the-protein-protein-interaction-network
#15
Hao Huang, Yuehan He, Wan Li, Wenqing Wei, Yiran Li, Ruiqiang Xie, Shanshan Guo, Yahui Wang, Jing Jiang, Binbin Chen, Junjie Lv, Nana Zhang, Lina Chen, Weiming He
Polycystic ovary syndrome (PCOS) is one of the most common endocrinological disorders in reproductive aged women. PCOS and Type 2 Diabetes (T2D) are closely linked in multiple levels and possess high pathobiological similarity. Here, we put forward a new computational approach based on the pathobiological similarity to identify PCOS potential drug target modules (PPDT-Modules) and PCOS potential drug targets in the protein-protein interaction network (PPIN). From the systems level and biological background, 1 PPDT-Module and 22 PCOS potential drug targets were identified, 21 of which were verified by literatures to be associated with the pathogenesis of PCOS...
June 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27155573/acid-ceramidase-and-the-treatment-of-ceramide-diseases-the-expanding-role-of-enzyme-replacement-therapy
#16
REVIEW
Edward H Schuchman
Ceramides are a diverse group of sphingolipids that play important roles in many biological processes. Acid ceramidase (AC) is one key enzyme that regulates ceramide metabolism. Early research on AC focused on the fact that it is the enzyme deficient in the rare genetic disorder, Farber Lipogranulomatosis. Recent research has revealed that deficiency of the same enzyme is responsible for a rare form of spinal muscular atrophy associated with myoclonic epilepsy (SMA-PME). Due to their diverse role in biology, accumulation of ceramides also has been implicated in the pathobiology of many other common diseases, including infectious lung diseases, diabetes, cancers and others...
September 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27126549/the-complex-metabolism-of-trimethylamine-in-humans-endogenous-and-exogenous-sources
#17
REVIEW
Jyoti Chhibber-Goel, Anamika Gaur, Varsha Singhal, Neeraj Parakh, Balram Bhargava, Amit Sharma
Trimethylamine (TMA) is a tertiary amine with a characteristic fishy odour. It is synthesised from dietary constituents, including choline, L-carnitine, betaine and lecithin by the action of microbial enzymes during both healthy and diseased conditions in humans. Trimethylaminuria (TMAU) is a disease typified by its association with the characteristic fishy odour because of decreased TMA metabolism and excessive TMA excretion. Besides TMAU, a number of other diseases are associated with abnormal levels of TMA, including renal disorders, cancer, obesity, diabetes, cardiovascular diseases and neuropsychiatric disorders...
April 29, 2016: Expert Reviews in Molecular Medicine
https://www.readbyqxmd.com/read/27112956/the-promise-and-challenge-of-therapeutic-microrna-silencing-in-diabetes-and-metabolic-diseases
#18
REVIEW
Praveen Sethupathy
MicroRNAs (miRNAs) are small, non-coding, RNA molecules that regulate gene expression. They have a long evolutionary history and are found in plants, viruses, and animals. Although initially discovered in 1993 in Caenorhabditis elegans, they were not appreciated as widespread and abundant gene regulators until the early 2000s. Studies in the last decade have found that miRNAs confer phenotypic robustness in the face of environmental perturbation, may serve as diagnostic and prognostic indicators of disease, underlie the pathobiology of a wide array of complex disorders, and represent compelling therapeutic targets...
June 2016: Current Diabetes Reports
https://www.readbyqxmd.com/read/27104844/cushing-s-disease-pathobiology-diagnosis-and-management
#19
Russell R Lonser, Lynnette Nieman, Edward H Oldfield
Cushing's disease (CD) is the result of excess secretion of adrenocorticotropic hormone (ACTH) by a benign monoclonal pituitary adenoma. The excessive secretion of ACTH stimulates secretion of cortisol by the adrenal glands, resulting in supraphysiological levels of circulating cortisol. The pathophysiological levels of cortisol are associated with hypertension, diabetes, obesity, and early death. Successful resection of the CD-associated ACTH-secreting pituitary adenoma is the treatment of choice and results in immediate biochemical remission with preservation of pituitary function...
February 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/27080977/a-nationally-representative-study-of-calcific-uremic-arteriolopathy-risk-factors
#20
Sagar U Nigwekar, Sophia Zhao, Julia Wenger, Jeffrey L Hymes, Franklin W Maddux, Ravi I Thadhani, Kevin E Chan
Accurate identification of risk factors for calcific uremic arteriolopathy (CUA) is necessary to develop preventive strategies for this morbid disease. We investigated whether baseline factors recorded at hemodialysis initiation would identify patients at risk for future CUA in a matched case-control study using data from a large dialysis organization. Hemodialysis patients with newly diagnosed CUA (n=1030) between January 1, 2010, and December 31, 2014, were matched by age, sex, and race in a 1:2 ratio to hemodialysis patients without CUA (n=2060)...
November 2016: Journal of the American Society of Nephrology: JASN
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