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Diabetes New Target

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https://www.readbyqxmd.com/read/29242563/ck2-modulates-adipocyte-insulin-signaling-and-is-up-regulated-in-human-obesity
#1
Christian Borgo, Gabriella Milan, Francesca Favaretto, Fabio Stasi, Roberto Fabris, Valentina Salizzato, Luca Cesaro, Anna Belligoli, Marta Sanna, Mirto Foletto, Luca Prevedello, Vincenzo Vindigni, Romeo Bardini, Arianna Donella-Deana, Roberto Vettor
Insulin plays a major role in glucose metabolism and insulin-signaling defects are present in obesity and diabetes. CK2 is a pleiotropic protein kinase implicated in fundamental cellular pathways and abnormally elevated in tumors. Here we report that in human and murine adipocytes CK2-inhibition decreases the insulin-induced glucose-uptake by counteracting Akt-signaling and GLUT4-translocation to the plasma membrane. In mice CK2 acts on insulin-signaling in adipose tissue, liver and skeletal muscle and its acute inhibition impairs glucose tolerance...
December 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29241884/the-use-of-decomposition-methods-in-real-world-treatment-benefits-evaluation-for-patients-with-type-2-diabetes-initiating-different-injectable-therapies-findings-from-the-initiator-study
#2
Lee Brekke, Erin Buysman, Michael Grabner, Xuehua Ke, Lin Xie, Onur Baser, Wenhui Wei
BACKGROUND: Determining characteristics of patients likely to benefit from a particular treatment could help physicians set personalized targets. OBJECTIVES: To use decomposition methodology on real-world data to identify the relative contributions of treatment effects and patients' baseline characteristics. METHODS: Decomposition analyses were performed on data from the Initiation of New Injectable Treatment Introduced after Antidiabetic Therapy with Oral-only Regimens (INITIATOR) study, a real-world study of patients with type 2 diabetes started on insulin glargine (GLA) or liraglutide (LIRA)...
December 2017: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/29240298/diabetic-macular-edema-innovative-technologies-and-economic-impact-new-opportunities-for-the-lombardy-region-healthcare-system
#3
Emanuela Foglia, Lucrezia Ferrario, Francesco Bandello, Camilla Ferri, Innocente Figini, Michela Franzin, Gianpiera Gambaro, Ugo Introini, Massimo Medaglia, Giovanni Staurenghi, Patrizia Tadini, Andrea Fomiatti, Davide Croce
PURPOSE: Diabetic macular edema (DME) is a leading cause of vision loss and blindness. The aim of this study was to evaluate the economic benefits of introducing additional alternative technologies (Dexamethasone intravitreal implant - DEX - and Aflibercept injections), compared with the historical scenario of Ranibizumab intravitreal injections. METHODS: A 3-year budget impact model was developed, taking into consideration the perspective of the Lombardy Region Healthcare Service (LRHS)...
December 14, 2017: Acta Ophthalmologica
https://www.readbyqxmd.com/read/29237358/on-the-relationship-of-anthranilic-derivatives-structure-and-the-fxr-farsenoid-x-receptor-agonist-activity
#4
Thales Kronenberger, Björn Windshügel, Carsten Wrenger, Kathia M Honorio, Vinicius G Maltarollo
Farsenoid X receptor (FXR) is a nuclear receptor related to lipid and glucose homeostasis and is considered an important molecular target to treatment of metabolic diseases as diabetes, dyslipidemia and liver cancer. Nowadays, there are several FXR agonists reported in the literature and some of it in clinical trials for liver disorders. Herein a compound series was employed to generate QSAR models to better understand the structural basis for FXR by anthranilic acid derivatives (AADs) agonists. Furthermore, here it is evaluated the inclusion of the standard deviation (SD) of EC50 values in QSAR models quality...
December 13, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29237342/racial-ethnic-disparities-in-late-stage-colorectal-cancer-among-hispanics-and-non-hispanic-whites-of-new-mexico
#5
Melissa Gonzales, Fares Qeadan, Shiraz I Mishra, Ashwani Rajput, Richard M Hoffman
INTRODUCTION: Hispanics in New Mexico are diagnosed with more later-stage colorectal cancer (CRC) than non-Hispanic Whites (NHW). Our study evaluated the interaction of race/ethnicity and risk factors for later-stage III and IV CRC among patients in New Mexico. METHOD: CRC patients ages 30 to 75 years ( n = 163, 46% Hispanic) completed a survey on key explanatory clinical, lifestyle, preventive health, and demographic variables for CRC risk. Adjusted logistic regression models examined whether these variables differentially contributed to later-stage CRC among NHW versus Hispanics...
December 2017: Hispanic Health Care International: the Official Journal of the National Association of Hispanic Nurses
https://www.readbyqxmd.com/read/29236298/leptin-a-new-therapeutic-target-for-treatment-of-diabetes-mellitus
#6
Kanwal Rehman, Muhammad Sajid Hamid Akash, Zunaira Alina
Leptin is an endogenous protein having 167 amino acids and is derived from adipocytes. It hass tertiary structure that resembles with that of the pro-inflammatory cytokines family. The fundamental role of leptin is to maintain the energy homeostasis with the aid of its counter hormone called ghrelin, known as the "hunger hormone". Small quantities of leptin are also present in various tissues like ovary, placenta, pituitary gland, mammary gland, skeletal muscle, stomach and lymphoid tissue. Expression of leptin is strongly associated with various inflammatory responses and immune system, and plays crucial role in the pathophysiology of obesity and development of diabetes mellitus (DM) and insulin resistance...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29234813/hormone-therapy-for-the-primary-prevention-of-chronic-conditions-in-postmenopausal-women-evidence-report-and-systematic-review-for-the-us-preventive-services-task-force
#7
Gerald Gartlehner, Sheila V Patel, Cynthia Feltner, Rachel Palmieri Weber, Rachel Long, Kelly Mullican, Erin Boland, Linda Lux, Meera Viswanathan
Importance: Postmenopausal status coincides with increased risks for chronic conditions such as heart disease, osteoporosis, cognitive impairment, or some types of cancers. Previously, hormone therapy was used for the primary prevention of these chronic conditions. Objective: To update evidence for the US Preventive Services Task Force on the benefits and harms of hormone therapy in reducing risks for chronic conditions. Data Sources: MEDLINE, Cochrane Library, EMBASE, and trial registries from June 1, 2011, through August 1, 2016...
December 12, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/29234032/heat-failure-phenotypes-induced-by-knockdown-of-dapit-in-zebrafish-a-new-insight-into-mechanism-of-dilated-cardiomyopathy
#8
Yoji Nagata, Masakazu Yamagishi, Tetsuo Konno, Chiaki Nakanishi, Yoshihiro Asano, Shin Ito, Yuri Nakajima, Osamu Seguchi, Noboru Fujino, Masa-Aki Kawashiri, Seiji Takashima, Masafumi Kitakaze, Kenshi Hayashi
The pathogenesis of heart failure associated with dilated cardiomyopathy (DCM) may result in part from adenosine triphosphate (ATP) dysregulation in the myocardium. Under these conditions, diabetes-associated protein in insulin-sensitive tissue (DAPIT), which is encoded by the upregulated during skeletal muscle growth 5 (USMG5) gene, plays a crucial role in energy production by mitochondrial ATP synthase. To determine whether USMG5 is related to the development of heart failure, we performed clinical and experimental studies...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29233848/g-protein-coupled-receptors-targeting-insulin-resistance-obesity-and-type-2-diabetes-mellitus
#9
REVIEW
Darren M Riddy, Philippe Delerive, Roger J Summers, Patrick M Sexton, Christopher J Langmead
G protein-coupled receptors (GPCRs) continue to be important discovery targets for the treatment of type 2 diabetes mellitus (T2DM). Many GPCRs are directly involved in the development of insulin resistance and β-cell dysfunction, and in the etiology of inflammation that can lead to obesity-induced T2DM. This review summarizes the current literature describing a number of well-validated GPCR targets, but also outlines several new and promising targets for drug discovery. We highlight the importance of understanding the role of these receptors in the disease pathology, and their basic pharmacology, which will pave the way to the development of novel pharmacological probes that will enable these targets to fulfill their promise for the treatment of these metabolic disorders...
January 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29233785/angiotensin-ii-receptor-blocker-valsartan-ameliorates-cardiac-fibrosis-partly-by-inhibiting-mir-21-expression-in-diabetic-nephropathy-mice
#10
Jinyang Wang, Lijun Duan, Yanbin Gao, Shuhong Zhou, Yongming Liu, Suhong Wei, Siqin An, Jing Liu, Liming Tian, Shaocheng Wang
Cardiac fibrosis with diabetic nephropathy (DN) is one of major diabetic complications. miR-21 and MMP-9 were closely associated with fibrosis diseases. Angiotensin II receptor blockers (ARB) have cardioprotective effects. However, it remains unclear whether miR-21 was involved in the mechanism of cardiac fibrosis with DN by target MMP-9 and ARB ameliorates cardiac fibrosis partly by inhibiting miR-21 expression. In this study, In Situ Hybridization(ISH), RT-PCR, cell transfection, western blotting and laser confocal telescope were used, respectively...
December 9, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29233722/county-level-contextual-factors-associated-with-diabetes-incidence-in-the-united-states
#11
Solveig A Cunningham, Shivani A Patel, Gloria L Beckles, Linda S Geiss, Neil Mehta, Hui Xie, Giuseppina Imperatore
PURPOSE: Health and administrative systems are facing spatial clustering in chronic diseases such as diabetes. This study explores how geographic distribution of diabetes in the United States is associated with socioeconomic and built environment characteristics and health-relevant policies. METHODS: We compiled nationally representative county-level data from multiple data sources. We standardized characteristics to a mean = 0 and a SD = 1 and modeled county-level age-adjusted diagnosed diabetes incidence in 2013 using 2-level hierarchical linear regression...
November 23, 2017: Annals of Epidemiology
https://www.readbyqxmd.com/read/29232436/cellular-versus-acellular-grafts-for-diabetic-foot-ulcers-altering-the-protocol-to-improve-recruitment-to-a-comparative-efficacy-trial
#12
Catherine N Tchanque-Fossuo, Sara E Dahle, Hadar Lev-Tov, Chin-Shang Li, R Rivkah Isseroff
Diabetic foot ulcers (DFUs) have a substantial impact on public health. The standard of care (SOC) for DFUs consists of a multidisciplinary approach involving glycemic control, wound care with debridement of necrotic tissue, application of a moist dressing, infection control, use of off-loading devices, and patient education. New therapeutic devices aim to target the extracellular matrix (ECM) that is impaired in DFU; however, there is insufficient data on the effectiveness of such therapies along with lack of evidence on their long-term effectiveness...
November 2017: Cutis; Cutaneous Medicine for the Practitioner
https://www.readbyqxmd.com/read/29229652/protocol-for-the-specialist-supervised-individualised-multifactorial-treatment-of-new-clinically-diagnosed-type-2-diabetes-in-general-practice-ida-a-prospective-controlled-multicentre-open-label-intervention-study
#13
Jacob Volmer Stidsen, Jens Steen Nielsen, Jan Erik Henriksen, Søren Gunnar Friborg, Reimar Wernich Thomsen, Thomas Bastholm Olesen, Michael Hecht Olsen, Henning Beck-Nielsen
INTRODUCTION: We present the protocol for a multifactorial intervention study designed to test whether individualised treatment, based on pathophysiological phenotyping and individualised treatment goals, improves type 2 diabetes (T2D) outcomes. METHODS AND ANALYSIS: We will conduct a prospective controlled multicentre open-label intervention study, drawing on the longitudinal cohort of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2). New clinically diagnosed patients with T2D in the intervention group will be assigned to receive individualised treatment by their general practitioner...
December 10, 2017: BMJ Open
https://www.readbyqxmd.com/read/29229552/caspase-6-is-a-dispensable-enabler-of-adult-mammalian-axonal-degeneration
#14
V Woo, C Cheng, A Duraikannu, A Chandrasekhar, K Purdy, J A Martinez, D W Zochodne
The progress of axonal degeneration (AxD) following injury or insult impacts both recovery from axonal transection and protection of axons from diverse insults, or axonopathy. Here we provide evidence that increases in capase-6 (Casp6) expression and action contribute to the progression of AxD. The expression of Casp6 protein and mRNA in distal branches of sensory axons undergoing AxD was confirmed. We developed and utilized a new model of axonopathy in live mice by serially visualizing the viability of cutaneous axons in the ear pinna that expressed an axonal YFP transgene, in response to capasaicin-induced AxD...
December 8, 2017: Neuroscience
https://www.readbyqxmd.com/read/29226155/views-and-experiences-of-new-zealand-women-with-gestational-diabetes-in-achieving-glycaemic-control-targets-the-views-study
#15
Ruth Martis, Julie Brown, Caroline A Crowther
Introduction: Optimal glycaemic control in women with gestational diabetes mellitus (GDM) reduces maternal and infant morbidity. Method: A survey was administered to women diagnosed with GDM to explore their views and experiences in achieving optimal glycaemic control. Results: Sixty women participated. Enablers included being taught to test capillary blood glucose in group settings where the health professional demonstrated this on themselves first (60, 100%); health professionals listening (41, 68%); being reminded to perform blood glucose testing (33, 55%); and being provided healthy meals by friends and family (28, 47%)...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/29225112/fisetin-a-bioactive-phytochemical-with-potential-for-cancer-prevention-and-pharmacotherapy
#16
REVIEW
Dharambir Kashyap, Ajay Sharma, Katrin Sak, Hardeep Singh Tuli, Harpal Singh Buttar, Anupam Bishayee
A wide variety of chronic diseases, such as neurodegenerative and cardiovascular disorders, diabetes mellitus, osteoarthtitis, obesity and various cancers, are now being treated with cost effective phytomedicines. Since synthetic medicines are very expensive, concerted efforts are being made in developing and poor countries to discover cost effective medicines for the treatment of non-communicable diseases (NCDs). Understanding the underlying mechanisms of bioactive medicines from natural sources would not only open incipient avenues for the scientific community and pharmaceutical industry to discover new drug molecules for the therapy of NCDs, but also help to garner knowledge for alternative therapeutic approaches for the management of chronic diseases...
December 7, 2017: Life Sciences
https://www.readbyqxmd.com/read/29224783/in%C3%A2-vivo-target-gene-activation-via-crispr-cas9-mediated-trans-epigenetic-modulation
#17
Hsin-Kai Liao, Fumiyuki Hatanaka, Toshikazu Araoka, Pradeep Reddy, Min-Zu Wu, Yinghui Sui, Takayoshi Yamauchi, Masahiro Sakurai, David D O'Keefe, Estrella Núñez-Delicado, Pedro Guillen, Josep M Campistol, Cheng-Jang Wu, Li-Fan Lu, Concepcion Rodriguez Esteban, Juan Carlos Izpisua Belmonte
Current genome-editing systems generally rely on inducing DNA double-strand breaks (DSBs). This may limit their utility in clinical therapies, as unwanted mutations caused by DSBs can have deleterious effects. CRISPR/Cas9 system has recently been repurposed to enable target gene activation, allowing regulation of endogenous gene expression without creating DSBs. However, in vivo implementation of this gain-of-function system has proven difficult. Here, we report a robust system for in vivo activation of endogenous target genes through trans-epigenetic remodeling...
November 30, 2017: Cell
https://www.readbyqxmd.com/read/29224103/sex-differences-and-role-of-estradiol-in-hypoglycemia-associated-counter-regulation
#18
Karen P Briski, Hussain N Alhamami, Ayed Alshamrani, Santosh K Mandal, Manita Shakya, Mostafa H H Ibrahim
Vital nerve cell functions, including maintenance of transmembrane voltage and information transfer, occur at high energy expense. Inadequate provision of the obligate metabolic fuel glucose exposes neurons to risk of dysfunction or injury. Clinical hypoglycemia rarely occurs in nondiabetic individuals but is an unfortunate regular occurrence in patients with type 1 or advanced insulin-treated type 2 diabetes mellitus. Requisite strict glycemic control, involving treatment with insulin, sulfonylureas, or glinides, can cause frequent episodes of iatrogenic hypoglycemia due to defective counter-regulation, including reduced glycemic thresholds and diminished magnitude of motor responses...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29222456/bmps-as-new-insulin-sensitizers-enhanced-glucose-uptake-in-mature-3t3-l1-adipocytes-via-ppar%C3%AE-and-glut4-upregulation
#19
Isabelle Schreiber, Gina Dörpholz, Claus-Eric Ott, Bjørt Kragesteen, Nancy Schanze, Cory Thomas Lee, Josef Köhrle, Stefan Mundlos, Karen Ruschke, Petra Knaus
Insulin-resistance is the main cause of type 2 diabetes. Here we describe the identification and characterization of BMP2 and BMP6 as new insulin-sensitizing growth factors in mature adipocytes. We show that BMP2 and BMP6 lead to enhanced insulin-mediated glucose uptake in both insulin-sensitive and -insensitive adipocytes. We exclude a direct effect of BMP2 or BMP6 on translocation of GLUT4 to the plasma membrane and demonstrate that these BMPs increase GLUT4 protein levels equipotent to Rosiglitazone. BMPs induce expression of PPARγ as the crucial mediator for the insulin-sensitizing effect...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29222111/rap1b-promotes-vegf-induced-endothelial-permeability-and-is-required-for-dynamic-regulation-of-endothelial-barrier
#20
Sribalaji Lakshmikanthan, Magdalena Sobczak, Sergio Li Calzi, Lynn Shaw, Maria B Grant, Magdalena Chrzanowska-Wodnicka
Vascular Endothelial Growth Factor (VEGF), a key angiogenic and permeability factor, plays an important role in new blood vessel formation. However, abnormal VEGF-induced VEGFR2 signaling leads to hyper-permeability. We demonstrated that Rap1, best known for promoting cell adhesion and vessel stability, is a critical regulator of VEGFR2-mediated angiogenic and shear-stress EC responses. To determine Rap1's role in endothelial barrier dynamics, we examined vascular permeability in EC-specific Rap1A- and Rap1B- knockout mice, cell-cell junction remodeling and EC monolayer resistivity in Rap1-deficient ECs under basal, inflammatory or elevated VEGF conditions...
December 8, 2017: Journal of Cell Science
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