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Target to treat diabetes

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https://www.readbyqxmd.com/read/28324867/blood-glucose-levels-and-glycaemic-burden-in-76-341-patients-attending-primary-care-bittersweet-findings-from-a-9-year-cohort-study
#1
Melinda J Carrington, Neale Cohen, Joshua F Wiley
AIMS: Diabetes care is principally applied in the primary care setting whereby we examined trends in glycaemic levels and goals and estimated avoidable glycaemic burden. METHODS: We retrieved glycated haemoglobin (HbA1C) results and glucose-lowering prescription records from a patient-based medical database during 2005-2013. There were 275,480 available HbA1C measurements from 76,341 individuals managed by 960 general practitioners from 321 clinics across Australia...
February 27, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28319060/the-anti-diabetic-drug-exenatide-a-glucagon-like-peptide-1-receptor-agonist-counteracts-hepatocarcinogenesis-through-camp-pka-egfr-stat3-axis
#2
M Zhou, M T S Mok, H Sun, A W Chan, Y Huang, A S L Cheng, G Xu
Epidemiological studies have demonstrated a close association of type 2 diabetes and hepatocellular carcinoma (HCC). Exenatide (Ex-4), a potent diabetes drug targeting glucagon-like peptide-1 receptor (GLP-1R), is protective against non-alcoholic fatty liver disease (NAFLD). However, the Ex-4 function and GLP-1R status have yet been explored in HCC. Herein we investigated the effect of Ex-4 in diethylnitrosamine (DEN)-treated mice consuming control or high-fat high-carbohydrate diet. Administration of Ex-4 significantly improved obesity-induced hyperglycemia and hyperlipidemia and reduced HCC multiplicity in obese DEN-treated mice, in which suppressed proliferation and induced apoptosis were confined to tumor cells...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28318634/dna-methyltransferase-1-may-be-a-therapy-target-for-attenuating-diabetic-nephropathy-and-podocyte-injury
#3
Li Zhang, Qianmei Zhang, Shuangxin Liu, Yuanhan Chen, Ruizhao Li, Ting Lin, Chunping Yu, Hong Zhang, Zhongshun Huang, Xinchen Zhao, Xiaofan Tan, Zhuo Li, Zhiming Ye, Jianchao Ma, Bin Zhang, Wenjian Wang, Wei Shi, Xinling Liang
The contribution of DNA methylation to diabetic nephropathy, especially the effect on podocyte integrity, is not clarified. Here we found that albuminuria in a db/db mouse model was markedly attenuated after treatment with a DNA methylation inhibitor. This was accompanied by alleviation of glomerular hypertrophy, mesangial matrix expansion, and podocyte injury. The expression of DNA methyltransferase 1 (Dnmt1), nuclear factor Sp1, and nuclear factor kappa B (NFκB)-p65 markedly increased in podocytes in vivo and in vitro under the diabetic state...
March 15, 2017: Kidney International
https://www.readbyqxmd.com/read/28315327/discovery-of-a-kelch-like-ech-associated-protein-1-inhibitory-tetrapeptide-and-its-structural-characterization
#4
Satoshi Sogabe, Kotaro Sakamoto, Yusuke Kamada, Akito Kadotani, Yasunori Fukuda, Jun-Ichi Sakamoto
Keap1 constitutively binds to the transcription factor Nrf2 to promote its degradation, resulting in negative modulation of genes involved in cellular protection against oxidative stress. Keap1 is increasingly recognized as an attractive target for treating diseases involving oxidative stress, including cancer, atherosclerosis, diabetes, arthritis, and neurodegeneration. We used phage-display peptide screening to identify a tetrapeptide showing moderate binding affinity, which inhibits the interaction between Nrf2 and Keap1...
March 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28314484/impact-of-health-policy-and-practice-on-finding-the-best-fit-for-patients-with-type-2-diabetes-after-metformin-failure-croatian-pilot-study
#5
Maja Cigrovski Berković, Davorka Herman Mahečić, Marina Gradišer, Ines Bilić-Ćurčić
AIM: We assessed the impact of clinical practice and health policy on the choice and efficacy of different second-line therapies for the treatment of type 2 diabetes (T2DM) after failure of metformin. METHODS: This retrospective database analysis included 200 patients with a follow-up period of 6 months. The primary end-point was achievement of HbA1c <7% and fasting (FBG) and postprandial glucose levels (PPG) <7.2mmol/L and <10mmol/L, respectively after three and six months of different add-on treatments...
March 14, 2017: Primary Care Diabetes
https://www.readbyqxmd.com/read/28303678/schooling-diabetes-use-of-continuous-glucose-monitoring-and-remote-monitors-in-the-home-and-school-settings
#6
Christine Erie, Michelle A Van Name, Kate Weyman, Stuart A Weinzimer, Jennifer Finnegan, Kristin Sikes, William V Tamborlane, Jennifer L Sherr
BACKGROUND: Despite significant advances in type 1 diabetes (T1D) management, achieving targeted glycemic control in pediatric patients remains a struggle. Continuous glucose monitoring (CGM) with remote access holds the promise to address this challenge by allowing caregivers to monitor glucose, even when the child is not directly under their supervision. OBJECTIVE: To explore real-time and remote CGM practices in homes and schools, including caregiver expectations regarding this technology...
March 17, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28298362/negative-regulation-of-smad1-pathway-and-collagen-iv-expression-by-store-operated-ca2-entry-in-glomerular-mesangial-cells
#7
Peiwen Wu, Yuezhong Ren, Yuhong Ma, Yanxia Wang, Hui Jiang, Sarika Chaudhari, Mark E Davis, Jonathan E Zuckerman, Rong Ma
Collagen IV (Col IV) is a major component of expanded glomerular extracellular matrix in diabetic nephropathy and Smad1 is a key molecule regulating Col IV expression in mesangial cells (MCs). The present study was conducted to determine if Smad1 pathway and Col IV protein abundance were regulated by store-operated Ca2+ entry (SOCE). In cultured human MCs, pharmacological inhibition of SOCE significantly increased the total amount of Smad1 protein. Activation of SOCE blunted high glucose-increased Smad1 protein content...
March 15, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28296239/stent-placement-in-the-superficial-femoral-and-proximal-popliteal-arteries-with-the-innova-self-expanding-bare-metal-stent-system
#8
Richard J Powell, Michael R Jaff, Herman Schroë, Andrew Benko, Juan Diaz-Cartelle, Stefan Müller-Hülsbeck
OBJECTIVES: The SuperNOVA trial was designed to evaluate performance of the Innova Vascular Self-Expanding Stent System (Boston Scientific, Marlborough, MA) for treating lesions in the femoropopliteal arteries. METHODS: Patients with chronic lower limb peripheral artery disease (Rutherford category 2, 3, or 4) and atherosclerotic lesions in the native superficial femoral and/or proximal popliteal artery (lengths 30-190 mm) were enrolled in this single-arm, multinational study...
March 15, 2017: Catheterization and Cardiovascular Interventions
https://www.readbyqxmd.com/read/28295931/salsalate-improves-glycemia-in-overweight-persons-with-diabetes-risk-factors-of-stable-statin-treated-cardiovascular-disease-a-30-month-randomized-placebo-controlled-trial
#9
Ninad Salastekar, Tanvi Desai, Thomas Hauser, Ernst J Schaefer, Kristen Fowler, Stacey Joseph, Steven Shoelson, Allison B Goldfine
Obesity related sub-acute chronic inflammation contributes to type 2 diabetes and atherosclerosis (1,2) . Multiple studies target inflammation to reduce dysglycemia and/or coronary heart disease (CHD) using diverse anti-inflammatory approaches. Several show salsalate, a pro-drug of salicylate, improves glycemia in type 2 diabetes, obesity, or impaired glucose tolerance. Durability of glycemic efficacy and safety of salsalate remains less well understood.
March 14, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28294857/-evaluation-of-antihypertensive-efficacy-and-patient-adherence-to-treatment-with-the-new-formulation-perindopril-arginine-orally-disintegrating-tablet-in-general-clinical-practice-optimum-program
#10
M G Glezer On Behalf Of The Optimum Program Participants
The purpose of this study was to evaluate the antihypertensive efficacy of perindopril arginine in the oral dispersible form of tablets, in clinical practice. MATERIALS AND METHODS: Post-marketing observational open program OPTIMUM was carried out from october 2014 to march 2015 year in 48 cities of the Russian Federation, 197 doctors. The observation included 957 patients. Prematurely retired from the study 17patients completed the observation in accordance with the protocol of 940 people...
April 2016: Kardiologiia
https://www.readbyqxmd.com/read/28294373/rationale-and-design-of-reduce-it-reduction-of-cardiovascular-events-with-icosapent-ethyl-intervention-trial
#11
Deepak L Bhatt, Ph Gabriel Steg, Eliot A Brinton, Terry A Jacobson, Michael Miller, Jean-Claude Tardif, Steven B Ketchum, Ralph T Doyle, Sabina A Murphy, Paresh N Soni, Rene A Braeckman, Rebecca A Juliano, Christie M Ballantyne
Residual cardiovascular risk persists despite statins, yet outcome studies of lipid-targeted therapies beyond low-density lipoprotein cholesterol (LDL-C) have not demonstrated added benefit. Triglyceride elevation is an independent risk factor for cardiovascular events. High-dose eicosapentaenoic acid (EPA) reduces triglyceride-rich lipoproteins without raising LDL-C. Omega-3s have postulated pleiotropic cardioprotective benefits beyond triglyceride-lowering. To date, no large, multinational, randomized clinical trial has proved that lowering triglycerides on top of statin therapy improves cardiovascular outcomes...
March 15, 2017: Clinical Cardiology
https://www.readbyqxmd.com/read/28290602/ajs1669-a-novel-small-molecule-muscle-glycogen-synthase-activator-improves-glucose-metabolism-and-reduces-body-fat-mass-in-mice
#12
Kazuhiro Nakano, Sen Takeshita, Noriko Kawasaki, Wataru Miyanaga, Yoriko Okamatsu, Mizuki Dohi, Tadakiyo Nakagawa
Impaired glycogen synthesis and turnover are common in insulin resistance and type 2 diabetes. As glycogen synthase (GS) is a key enzyme involved in the synthetic process, it presents a promising therapeutic target for the treatment of type 2 diabetes. In the present study, we identified a novel, potent and orally available GS activator AJS1669 {sodium 2-[[5-[[4-(4,5-difluoro-2-methylsulfanyl-phenyl)phenoxy] methyl]furan-2-carbonyl]-(2-furylmethyl)amino] acetate}. In vitro, we performed a glycogen synthase 1 (GYS1) activation assay for screening GS activators and identified that the activity of AJS1669 was further potentiated in the presence of glucose-6-phosphate (G6P)...
March 7, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28289653/efficacy-of-low-and-moderate-intensity-statins-for-achieving-low-density-lipoprotein-cholesterol-targets-in-thai-type-2-diabetic-patients
#13
Nuntakorn Thongtang, Chaiyut Sitthananun, Sutin Sriussadaporn, Wannee Nitiyanant
BACKGROUND: Low dose statins are commonly used among Asians, because plasma low-density lipoprotein cholesterol (LDL-C) reductions similar to those observed in Westerners are achieved at lower doses. We aimed to assess the efficacy of low- and moderate-intensity statins for achieving plasma lipid targets in Thai type2 diabetes (T2D) and to evaluate factors associated with greater LDL-C reduction by statins. METHODS: T2D patients who were treated with low- and moderate-intensity statins at the Siriraj Diabetes Clinic during the January 2013 to December 2014 study period were eligible for inclusion(n = 978), 400 patients were randomly recruited...
2017: Journal of Diabetes and Metabolic Disorders
https://www.readbyqxmd.com/read/28289375/hypoxia-inducible-factor-1%C3%AE-target-genes-contribute-to-retinal-neuroprotection
#14
REVIEW
Lin Cheng, Honghua Yu, Naihong Yan, Kunbei Lai, Mengqing Xiang
Hypoxia-inducible factor (HIF) is a transcription factor that facilitates cellular adaptation to hypoxia and ischemia. Long-standing evidence suggests that one isotype of HIF, HIF-1α, is involved in the pathogenesis of various solid tumors and cardiac diseases. However, the role of HIF-1α in retina remains poorly understood. HIF-1α has been recognized as neuroprotective in cerebral ischemia in the past two decades. Additionally, an increasing number of studies has shown that HIF-1α and its target genes contribute to retinal neuroprotection...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28284664/high-baseline-c-reactive-protein-levels-predict-partial-type-2-diabetes-mellitus-remission-after-biliopancreatic-diversion
#15
A Bonaventura, L Liberale, F Carbone, N Scopinaro, G Camerini, F S Papadia, R Cordera, F Dallegri, G F Adami, F Montecucco
BACKGROUND AND AIMS: Several studies demonstrated that surgery can improve inflammation parameters, such as C-reactive protein (CRP). Few biomarkers have been investigated to potentially predict type 2 diabetes mellitus (T2DM) remission. We aimed at determining whether pre-surgery serum CRP levels could predict T2DM remission after 3 years in patients undergoing bariatric surgery, especially biliopancreatic diversion (BPD). METHODS AND RESULTS: This study was conducted from 2007 to 2009 at the Surgical Department of the University of Genoa, Italy...
February 3, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/28283687/impact-of-gain-of-function-mutations-in-the-low-density-lipoprotein-receptor-related-protein-5-lrp5-on-glucose-and-lipid-homeostasis
#16
D Foer, M Zhu, R L Cardone, C Simpson, R Sullivan, S Nemiroff, G Lee, R G Kibbey, K F Petersen, K L Insogna
LRP5 loss-of-function mutations have been shown to cause profound osteoporosis and have been associated with impaired insulin sensitivity and dysregulated lipid metabolism. We hypothesized that gain-of-function mutations in LRP5 would also affect these parameters. We therefore studied individuals with LRP5 gain-of-function mutations exhibiting high bone mass (HBM) phenotypes and found that while there was no detected change in insulin sensitivity, there was a significant reduction in serum LDL. INTRODUCTION: Wnt signaling through LRP5 represents a newly appreciated metabolic pathway, which potentially represents a target for drug discovery in type 2 diabetes and hyperlipidemia...
March 10, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28280903/microrna-21-targets-bcl2-mrna-to-increase-apoptosis-in-rat-and-human-beta-cells
#17
Emily K Sims, Alexander J Lakhter, Emily Anderson-Baucum, Tatsuyoshi Kono, Xin Tong, Carmella Evans-Molina
AIMS/HYPOTHESIS: The role of beta cell microRNA (miR)-21 in the pathophysiology of type 1 diabetes has been controversial. Here, we sought to define the context of beta cell miR-21 upregulation in type 1 diabetes and the phenotype of beta cell miR-21 overexpression through target identification. METHODS: Islets were isolated from NOD mice and mice treated with multiple low doses of streptozotocin, as a mouse model of diabetes. INS-1 832/13 beta cells and human islets were treated with IL-1β, IFN-γ and TNF-α to mimic the milieu of early type 1 diabetes...
March 9, 2017: Diabetologia
https://www.readbyqxmd.com/read/28280900/paracrine-gaba-and-insulin-regulate-pancreatic-alpha-cell-proliferation-in-a-mouse-model-of-type-1-diabetes
#18
Allen L Feng, Yun-Yan Xiang, Le Gui, Gesthika Kaltsidis, Qingping Feng, Wei-Yang Lu
AIMS/HYPOTHESIS: This study aimed to elucidate the mechanism of increased proliferation of alpha cells in recent-onset type 1 diabetes. Pancreatic beta cells express GAD and produce γ-aminobutyric acid (GABA), which inhibits alpha cell secretion of glucagon. We explored the roles of GABA in alpha cell proliferation in conditions corresponding to type 1 diabetes in a mouse model and in vitro. METHODS: Type 1 diabetes was induced by injecting the mice with streptozotocin (STZ)...
March 9, 2017: Diabetologia
https://www.readbyqxmd.com/read/28279889/polysaccharide-from-angelica-sinensis-ameliorates-high-fat-diet-and-stz-induced-hepatic-oxidative-stress-and-inflammation-in-diabetic-mice-by-activating-the-sirt1-ampk-pathway
#19
Kaiping Wang, Zhuohong Tang, Jinglin Wang, Peng Cao, Qiang Li, Weizhi Shui, Hongjing Wang, Ziming Zheng, Yu Zhang
Polysaccharide from Angelica sinensis (Oliv.) Diels (ASP) possesses many bioactivities, such as hematopoiesis, anti-inflammation, antioxidation and metabolism regulation. The aim of this study was to investigate the mechanisms underlying the protection of a combination of high-fat diet and streptozotocin-induced liver damage in diabetic Balb/c mice by ASP. Results showed that ASP had beneficial effects on ameliorating hyperglycemia, dyslipidemia and liver injury. Moreover, mechanistic study for the liver-protective role in vivo demonstrated that ASP enhanced the activities of superoxide dismutase and glutathione peroxidase and increased the glutathione content, which resulted in the reduction of hepatic reactive oxygen species (ROS) and malondialdehyde, and reduced the protein expression levels of liver IKKα/NF-κB/p-IκBα and the concentrations of serum tumor necrosis factor-α/interleukin-6...
February 10, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28275550/svmrfe-based-approach-for-prediction-of-most-discriminatory-gene-target-for-type-ii-diabetes
#20
Atul Kumar, D Jeya Sundara Sharmila, Sachidanand Singh
Type II diabetes is a chronic condition that affects the way our body metabolizes sugar. The body's important source of fuel is now becoming a chronic disease all over the world. It is now very necessary to identify the new potential targets for the drugs which not only control the disease but also can treat it. Support vector machines are the classifier which has a potential to make a classification of the discriminatory genes and non-discriminatory genes. SVMRFE a modification of SVM ranks the genes based on their discriminatory power and eliminate the genes which are not involved in causing the disease...
June 2017: Genomics Data
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