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Diabetes transition

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https://www.readbyqxmd.com/read/28334950/downstream-targets-of-gwas-detected-genes-for-breast-lung-and-prostate-and-colon-cancer-converge-to-g1-s-transition-pathway
#1
Olga Y Gorlova, Eugene I Demidenko, Christopher I Amos, Ivan P Gorlov
Genome-wide association studies (GWASs) identified over 500 single nucleotide polymorphisms (SNPs) influencing cancer risk. It is logical to expect the cancer-associated genes to cluster in pathways directly involved in carcinogenesis, e.g. cell cycle. Nevertheless, analyses of the GWAS-detected cancer risk genes usually show no or weak enrichment by known cancer genes.We hypothesized that GWAS-detected cancer risk-associated genes function as upstream regulators of the genes directly involved in carcinogenesis...
March 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334027/metformin-inhibits-gastric-cancer-cells-metastatic-traits-through-suppression-of-epithelial-mesenchymal-transition-in-a-glucose-independent-manner
#2
Shiva Valaee, Mohammad Mehdi Yaghoobi, Mehdi Shamsara
Epithelial-mesenchymal transition (EMT), which is mainly recognized by upregulation of mesenchymal markers and movement of cells, is a critical stage occurred during embryo development and spreading cancerous cells. Metformin is an antidiabetic drug used in treatment of type 2 diabetes. EMT inhibitory effect of metformin has been studied in several cancers; however, it remains unknown in gastric cancer. The aim of the present study was to investigate the metformin effects on inhibition of EMT-related genes as well as migration and invasion of AGS gastric cancer cell line...
2017: PloS One
https://www.readbyqxmd.com/read/28333382/regulation-and-function-of-extracellular-nicotinamide-phosphoribosyltransferase-visfatin
#3
Federico Carbone, Luca Liberale, Aldo Bonaventura, Alessandra Vecchiè, Matteo Casula, Michele Cea, Fiammetta Monacelli, Irene Caffa, Santina Bruzzone, Fabrizio Montecucco, Alessio Nencioni
Nicotinamide phosphoribosyltransferase (NAMPT) is an adipokine-enzyme, which was described as to play bioactivities both in the intracellular and in the extracellular environment. However, while the functions of intracellular NAMPT (iNAMPT) are well known, much less is known on extracellular NAMPT (eNAMPT), also called visfatin or pre-B cell colony-enhancing factor. iNAMPT catalyzes the rate-limiting step in the NAD+ biosynthesis pathway from nicotinamide. Its inhibition severely reduces intracellular NAD+ levels, achieving anti-inflammatory and anti-cancer effects...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28325798/management-of-inpatient-hyperglycemia-and-diabetes-in-older-adults
#4
Guillermo E Umpierrez, Francisco J Pasquel
Adults aged 65 years and older are the fastest growing segment of the U.S. population, and their number is expected to double to 89 million between 2010 and 2050. The prevalence of diabetes in hospitalized adults aged 65-75 years and over 80 years of age has been estimated to be 20% and 40%, respectively. Similar to general populations, the presence of hyperglycemia and diabetes in elderly patients is associated with increased risk of hospital complications, longer length of stay, and increased mortality compared with subjects with normoglycemia...
April 2017: Diabetes Care
https://www.readbyqxmd.com/read/28323912/sex-hormones-and-cardiometabolic-health-role-of-estrogen-and-estrogen-receptors
#5
Deborah Clegg, Andrea L Hevener, Kerrie L Moreau, Eugenia Morselli, Alfredo Criollo, Rachael E Van Pelt, Victoria J Vieira-Potter
With increased life expectancy, women will spend over three decades of life post-menopause. The menopausal transition increases susceptibility to metabolic diseases such as obesity, diabetes, cardiovascular disease, and cancer. Thus, it is more important than ever to develop effective hormonal treatment strategies to protect aging women. Understanding the role of estrogens, and their biological actions mediated by estrogen receptors (ERs), in the regulation of cardiometabolic health is of paramount importance to discover novel targeted therapeutics...
February 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28315789/involvement-of-epithelial-mesenchymal-transition-afforded-by-activation-of-lox-1-tgf-%C3%AE-1-klf6-signaling-pathway-in-diabetic-pulmonary-fibrosis
#6
Xiao-Zhou Zou, Zhi-Cheng Gong, Ting Liu, Fang He, Tian-Tian Zhu, Dai Li, Wei-Fang Zhang, Jun-Lin Jiang, Chang-Ping Hu
BACKGROUND AND OBJECTIVE: Diabetic pulmonary fibrosis is a severe disease that increases mortality risk of diabetes. However, the molecular mechanisms leading to pulmonary fibrosis in diabetes are poorly understood. This study investigated the roles of epithelial-mesenchymal transition (EMT) and the associated molecular mechanisms in streptozotocin (STZ)-induced rat pulmonary fibrosis. METHODS: The rat model of diabetic pulmonary fibrosis was established by intraperitoneal injection of a single dose of STZ (35 mg/kg)...
March 15, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28315733/wt1-ameliorates-podocyte-injury-via-repression-of-ezh2-%C3%AE-catenin-pathway-in-diabetic-nephropathy
#7
Jiao Wan, Xiaoyan Hou, Zhanmei Zhou, Jian Geng, Jianwei Tian, Jing Nie, Xiaoyan Bai
Epigenetic modulation of podocyte injury plays a pivotal role in diabetic nephropathy (DN). Wilm's tumor 1 (WT1) has been found to have opposing roles with β-catenin in podocyte biology. Herein, we asked whether the histone methyltransferase enzyme enhancer of zeste homolog 2 (EZH2) promotes WT1-induced podocyte injury via β-catenin activation and the underlying mechanisms. We found that WT1 antagonized EZH2 and ameliorated β-catenin-mediated podocyte injury as demonstrated by attenuated podocyte mesenchymal transition, maintenance of podocyte architectural integrity, decreased podocyte apoptosis and oxidative stress...
March 15, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28314624/cerebral-white-matter-hypoperfusion-increases-with-small-vessel-disease-burden-data-from-the-third-international-stroke-trial
#8
Francesco Arba, Grant Mair, Trevor Carpenter, Eleni Sakka, Peter A G Sandercock, Richard I Lindley, Domenico Inzitari, Joanna M Wardlaw
BACKGROUND: Leukoaraiosis is associated with impaired cerebral perfusion, but the effect of individual and combined small-vessel disease (SVD) features on white matter perfusion is unclear. METHODS: We studied patients recruited with perfusion imaging in the Third International Stroke Trial. We rated individual SVD features (leukoaraiosis, lacunes) and brain atrophy on baseline plain computed tomography or magnetic resonance imaging. Separately, we assessed white matter at the level of the lateral ventricles in the cerebral hemisphere contralateral to the stroke for visible areas of hypoperfusion (present or absent) on 4 time-based perfusion imaging parameters...
March 14, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/28302101/preventing-diabetes-in-obese-latino-youth-with-prediabetes-a-study-protocol-for-a-randomized-controlled-trial
#9
Erica G Soltero, Yolanda P Konopken, Micah L Olson, Colleen S Keller, Felipe G Castro, Allison N Williams, Donald L Patrick, Stephanie Ayers, Houchun H Hu, Matthew Sandoval, Janiel Pimentel, William C Knowler, Kevin D Frick, Gabriel Q Shaibi
BACKGROUND: Obese Latino adolescents are disproportionately impacted by insulin resistance and type 2 diabetes. Prediabetes is an intermediate stage in the pathogenesis of type 2 diabetes and represents a critical opportunity for intervention. However, to date, no diabetes prevention studies have been conducted in obese Latino youth with prediabetes, a highly vulnerable and underserved group. Therefore, we propose a randomized-controlled trial to test the short-term (6-month) and long-term (12-month) efficacy of a culturally-grounded, lifestyle intervention, as compared to usual care, for improving glucose tolerance and reducing diabetes risk in 120 obese Latino adolescents with prediabetes...
March 16, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28300592/new-peptide-inhibitors-modulate-the-self-assembly-of-islet-amyloid-polypeptide-residues-11-20-in-vitro
#10
Yexuan Mao, Lanlan Yu, Ran Yang, Chuanguo Ma, Lingbo Qu, Peter de B Harrington
The structural transition and misfolding of human islet amyloid polypeptide may cause a common metabolic disease Type 2 diabetes mellitus. Seventeen peptides have been synthesized, possessing different lengths, compositions, and peptide conformation. In this study, the mechanism of these peptides on inhibiting the formation of hIAPP11-20 amyloid fibrils was investigated using a conventional ThT fluorescence assay and microscale thermophoresis. The results showed that short peptides AT, SA, RF, KS, KT and KN, and cyclic peptides cyclic-KS, cyclic-KT and cyclic-KN displayed considerable inhibitory effect on hIAPP11-20 fibril formation and a strong affinity for hIAPP11-20...
March 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28299341/hepatic-cholesterol-25-hydroxylase-overexpression-improves-systemic-insulin-sensitivity-in-mice
#11
Britta Noebauer, Alexander Jais, Jelena Todoric, Klaus Gossens, Hedwig Sutterlüty-Fall, Elisa Einwallner
Obesity is a major risk factor for several diseases including diabetes, heart disease, and some forms of cancer and due to its rapidly increasing prevalence it has become one of the biggest problems medicine is facing today. All the more surprising, a substantial percentage of obese patients are metabolically healthy when classified based on insulin resistance and systemic inflammation. Oxysterols are naturally occurring molecules that play important role in various metabolic and inflammatory processes and their levels are elevated in patients suffering from obesity and diabetes...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28290581/deconvolution-of-heterogeneous-wound-tissue-samples-into-relative-macrophage-phenotype-composition-via-models-based-on-gene-expression
#12
Nicole M Ferraro, Will Dampier, Michael S Weingarten, Kara L Spiller
Macrophages, the primary cell of the innate immune system, act on a spectrum of phenotypes that correspond to diverse functions. Dysregulation of macrophage phenotype is associated with many diseases. In particular, defective transition from pro-inflammatory (M1) to anti-inflammatory (M2) behavior has been implicated as a potential source of sustained inflammation that prevents healing of chronic wounds such as diabetic ulcers. In order to design effective treatments, an understanding of the relative presence of macrophage phenotypes during tissue repair is necessary...
March 14, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28286049/insulin-signaling-regulates-the-foxm1-plk1-cenp-a-pathway-to-promote-adaptive-pancreatic-%C3%AE-%C3%A2-cell-proliferation
#13
Jun Shirakawa, Megan Fernandez, Tomozumi Takatani, Abdelfattah El Ouaamari, Prapaporn Jungtrakoon, Erin R Okawa, Wei Zhang, Peng Yi, Alessandro Doria, Rohit N Kulkarni
Investigation of cell-cycle kinetics in mammalian pancreatic β cells has mostly focused on transition from the quiescent (G0) to G1 phase. Here, we report that centromere protein A (CENP-A), which is required for chromosome segregation during the M-phase, is necessary for adaptive β cell proliferation. Receptor-mediated insulin signaling promotes DNA-binding activity of FoxM1 to regulate expression of CENP-A and polo-like kinase-1 (PLK1) by modulating cyclin-dependent kinase-1/2. CENP-A deposition at the centromere is augmented by PLK1 to promote mitosis, while knocking down CENP-A limits β cell proliferation and survival...
February 26, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28277542/microrna-27a-promotes-podocyte-injury-via-ppar%C3%AE-mediated-%C3%AE-catenin-activation-in-diabetic-nephropathy
#14
Zhanmei Zhou, Jiao Wan, Xiaoyan Hou, Jian Geng, Xiao Li, Xiaoyan Bai
Podocyte injury has a pivotal role in the pathogenesis of diabetic nephropathy (DN). MicroRNA-27a (miR-27a), peroxisome proliferator-activated receptor γ (PPARγ) and β-catenin pathways have been involved in the pathogenesis of DN. Herein, we asked whether miR-27a mediates podocyte injury through PPARγ/β-catenin signaling in DN. The functional relevance of miR-27a, PPARγ and β-catenin were investigated in cultured podocytes and glomeruli of diabetic rats and patients using in vitro and in vivo approaches...
March 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28276155/dissecting-copper-homeostasis-in-diabetes-mellitus
#15
REVIEW
Jennifer Lowe, Rosilane Taveira-da-Silva, Elaine Hilário-Souza
Diabetes Mellitus (DM) is characterized by elevated blood glucose levels (hyperglycemia). It can occur due to impaired secretion or action of the hormone insulin, which is produced by pancreatic beta-cells to promote the entry of glucose into the cells. It is known that hyperglycemia has an important role in the production of reactive oxygen species in all types of DM and that an imbalance of transition metal as Cu and Fe plays a pivotal role in stimulating the oxidative stress. Different levels of some transition metals, as Cu, Fe, Mn, and Zn has been reported comparing diabetic animal models with the control group...
March 9, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28274941/supporting-insulin-initiation-in-type-2-diabetes-in-primary-care-results-of-the-stepping-up-pragmatic-cluster-randomised-controlled-clinical-trial
#16
John Furler, David O'Neal, Jane Speight, Jo-Anne Manski-Nankervis, Alexandra Gorelik, Elizabeth Holmes-Truscott, Louise Ginnivan, Doris Young, James Best, Elizabeth Patterson, Danny Liew, Leonie Segal, Carl May, Irene Blackberry
Objective To compare the effectiveness of a novel model of care ("Stepping Up") with usual primary care in normalising insulin initiation for type 2 diabetes, leading to improved glycated haemoglobin (HbA1c) levels.Design Cluster randomised controlled trial.Setting Primary care practices in Victoria, Australia, with a practice nurse and at least one consenting eligible patient (HbA1c ≥7.5% with maximal oral treatment).Participants 266 patients with type 2 diabetes and 74 practices (mean cluster size 4 (range 1-8) patients), followed up for 12 months...
March 8, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28274869/effective-inhibition-of-protein-glycation-by-combinatorial-usage-of-limonene-and-aminoguanidine-through-differential-and-synergistic-mechanisms
#17
Madhav M Joglekar, Laxman N Bavkar, Srinivas Sistla, Akalpita U Arvindekar
Protein glycation is a major mechanism for establishing secondary complication in diabetes mellitus. Effective inhibition of this process can prevent progression of the disorder into secondary complications. Aminoguanidine (AMG) and limonene (LM) are known protein glycation inhibitors. The aim of the present study was to demonstrate their differential mechanisms of action and to study whether combinatorial therapy can act synergistically and lower dosage, and thereby lower toxicity in treatment of secondary complications in diabetes...
March 6, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28274680/a-retrospective-review-of-insulin-requirements-in-patients-using-u-500-insulin-hospitalized-to-a-veterans-affairs-hospital
#18
Rohit Kedia, Cyrus Desouza, Lynette M Smith, Vijay Shivaswamy
AIMS: The aim of this study was to compare the changes in the total daily dose (TDD) of insulin of patients on U-500 insulin; before hospitalization, during hospitalization and six weeks after discharge. METHODS: A retrospective chart review of veterans with type 2 diabetes receiving U-500 insulin in the ambulatory setting and who were admitted between 2012 and 2015 was performed. During hospitalization, patients were transitioned to receive U-100 insulin (detemir or glargine for basal and aspart for bolus)...
February 21, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28271846/non-communicable-disease-syndemics-poverty-depression-and-diabetes-among-low-income-populations
#19
REVIEW
Emily Mendenhall, Brandon A Kohrt, Shane A Norris, David Ndetei, Dorairaj Prabhakaran
The co-occurrence of health burdens in transitioning populations, particularly in specific socioeconomic and cultural contexts, calls for conceptual frameworks to improve understanding of risk factors, so as to better design and implement prevention and intervention programmes to address comorbidities. The concept of a syndemic, developed by medical anthropologists, provides such a framework for preventing and treating comorbidities. The term syndemic refers to synergistic health problems that affect the health of a population within the context of persistent social and economic inequalities...
March 4, 2017: Lancet
https://www.readbyqxmd.com/read/28270406/akr1b1-promotes-basal-like-breast-cancer-progression-by-a-positive-feedback-loop-that-activates-the-emt-program
#20
Xuebiao Wu, Xiaoli Li, Qiang Fu, Qianhua Cao, Xingyu Chen, Mengjie Wang, Jie Yu, Jingpei Long, Jun Yao, Huixin Liu, Danping Wang, Ruocen Liao, Chenfang Dong
Basal-like breast cancer (BLBC) is associated with high-grade, distant metastasis and poor prognosis. Elucidating the determinants of aggressiveness in BLBC may facilitate the development of novel interventions for this challenging disease. In this study, we show that aldo-keto reductase 1 member B1 (AKR1B1) overexpression highly correlates with BLBC and predicts poor prognosis in breast cancer patients. Mechanistically, Twist2 transcriptionally induces AKR1B1 expression, leading to nuclear factor κB (NF-κB) activation...
March 7, 2017: Journal of Experimental Medicine
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