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Pathobiology of diabetes

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https://www.readbyqxmd.com/read/27916653/pericytes-an-overlooked-player-in-vascular-pathobiology
#1
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 19(th) 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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...
April 22, 2016: Journal of Neurosurgery
https://www.readbyqxmd.com/read/27080977/a-nationally-representative-study-of-calcific-uremic-arteriolopathy-risk-factors
#15
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
https://www.readbyqxmd.com/read/27076423/brain-wide-insulin-resistance-tau-phosphorylation-changes-and-hippocampal-neprilysin-and-amyloid-%C3%AE-alterations-in-a-monkey-model-of-type-1-diabetes
#16
Jose Morales-Corraliza, Harrison Wong, Matthew J Mazzella, Shaoli Che, Sang Han Lee, Eva Petkova, Janice D Wagner, Scott E Hemby, Stephen D Ginsberg, Paul M Mathews
UNLABELLED: Epidemiological findings suggest that diabetic individuals are at a greater risk for developing Alzheimer's disease (AD). To examine the mechanisms by which diabetes mellitus (DM) may contribute to AD pathology in humans, we examined brain tissue from streptozotocin-treated type 1 diabetic adult male vervet monkeys receiving twice-daily exogenous insulin injections for 8-20 weeks. We found greater inhibitory phosphorylation of insulin receptor substrate 1 in each brain region examined of the diabetic monkeys when compared with controls, consistent with a pattern of brain insulin resistance that is similar to that reported in the human AD brain...
April 13, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27073420/pathophysiology-of-valvular-heart-disease
#17
Y I Zeng, Rongrong Sun, Xianchi Li, Min Liu, Shuang Chen, Peiying Zhang
Valvular heart disease (VHD) is caused by either damage or defect in one of the four heart valves, aortic, mitral, tricuspid or pulmonary. Defects in these valves can be congenital or acquired. Age, gender, tobacco use, hypercholesterolemia, hypertension, and type II diabetes contribute to the risk of disease. VHD is an escalating health issue with a prevalence of 2.5% in the United States alone. Considering the likely increase of the aging population worldwide, the incidence of acquired VHD is expected to increase...
April 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27026810/adiponectin-levels-predict-prediabetes-risk-the-pathobiology-of-prediabetes-in-a-biracial-cohort-pop-abc-study
#18
Yunna Jiang, Ibiye Owei, Jim Wan, Sotonte Ebenibo, Samuel Dagogo-Jack
BACKGROUND: Adiponectin levels display ethnic disparities, and are inversely associated with the risk of type 2 diabetes (T2DM). However, the association of adiponectin with prediabetes risk in diverse populations has not been well-studied. Here, we assessed baseline adiponectin levels in relation to incident prediabetes in a longitudinal biracial cohort. RESEARCH DESIGN AND METHODS: The Pathobiology of Prediabetes in A Biracial Cohort study followed non-diabetic offspring of parents with T2DM for the occurrence of prediabetes, defined as impaired fasting glucose and/or impaired glucose tolerance...
2016: BMJ Open Diabetes Research & Care
https://www.readbyqxmd.com/read/26920376/genetic-overlap-between-multiple-sclerosis-and-several-cardiovascular-disease-risk-factors
#19
Yunpeng Wang, Steffan D Bos, Hanne F Harbo, Wesley K Thompson, Andrew J Schork, Francesco Bettella, Aree Witoelar, Benedicte A Lie, Wen Li, Linda K McEvoy, Srdjan Djurovic, Rahul S Desikan, Anders M Dale, Ole A Andreassen
BACKGROUND: Epidemiological findings suggest a relationship between multiple sclerosis (MS) and cardiovascular disease (CVD) risk factors, although the nature of this relationship is not well understood. OBJECTIVE: We used genome-wide association study (GWAS) data to identify shared genetic factors (pleiotropy) between MS and CVD risk factors. METHODS: Using summary statistics from a large, recent GWAS (total n > 250,000 individuals), we investigated overlap in single nucleotide polymorphisms (SNPs) associated with MS and a number of CVD risk factors including triglycerides (TG), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, body mass index, waist-to-hip ratio, type 2 diabetes, systolic blood pressure, and C-reactive protein level...
February 26, 2016: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/26860342/cellular-and-molecular-mechanisms-of-aki
#20
Anupam Agarwal, Zheng Dong, Raymond Harris, Patrick Murray, Samir M Parikh, Mitchell H Rosner, John A Kellum, Claudio Ronco
In this article, we review the current evidence for the cellular and molecular mechanisms of AKI, focusing on epithelial cell pathobiology and related cell-cell interactions, using ischemic AKI as a model. Highlighted are the clinical relevance of cellular and molecular targets that have been investigated in experimental models of ischemic AKI and how such models might be improved to optimize translation into successful clinical trials. In particular, development of more context-specific animal models with greater relevance to human AKI is urgently needed...
May 2016: Journal of the American Society of Nephrology: JASN
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