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Diabetes New Target

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https://www.readbyqxmd.com/read/28330905/secretogranin-iii-as-a-disease-associated-ligand-for-antiangiogenic-therapy-of-diabetic-retinopathy
#1
Michelle E LeBlanc, Weiwen Wang, Xiuping Chen, Nora B Caberoy, Feiye Guo, Chen Shen, Yanli Ji, Hong Tian, Hui Wang, Rui Chen, Wei Li
Diabetic retinopathy (DR) is a leading cause of vision loss with retinal vascular leakage and/or neovascularization. Current antiangiogenic therapy against vascular endothelial growth factor (VEGF) has limited efficacy. In this study, we applied a new technology of comparative ligandomics to diabetic and control mice for the differential mapping of disease-related endothelial ligands. Secretogranin III (Scg3) was discovered as a novel disease-associated ligand with selective binding and angiogenic activity in diabetic but not healthy vessels...
March 22, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28325698/factors-associated-with-antidiabetic-medication-non-adherence-in-patients-with-incident-comorbid-depression
#2
Carlotta Lunghi, Arsène Zongo, Jocelyne Moisan, Jean-Pierre Grégoire, Line Guénette
AIM: To identify factors associated with antidiabetic drug (AD) non-adherence among patients with type 2 diabetes and depression. STUDY DESIGN AND SETTINGS: We conducted a population-based retrospective cohort study among new AD users with a diagnosis of depression following AD initiation. We used public health insurance data from Quebec. The dependent variable was non-adherence (i.e., <90% of days covered by ≥1AD) in the year after a depression diagnosis. Different sociodemographic, clinical and medication-related variables were assessed as potential factors of non-adherence to AD treatment...
March 12, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28324102/duodenal-mucosa-of-patients-with-type-1-diabetes-shows-distinctive-inflammatory-profile-and-microbiota
#3
Silvia Pellegrini, Valeria Sordi, Andrea Mario Bolla, Diego Saita, Roberto Ferrarese, Filippo Canducci, Massimo Clementi, Francesca Invernizzi, Alberto Mariani, Riccardo Bonfanti, Graziano Barera, Pier Alberto Testoni, Claudio Doglioni, Emanuele Bosi, Lorenzo Piemonti
Context: Increasing evidences suggest a correlation between gut and type 1 diabetes (T1D). Objective: The objective of this study is to evaluate the gut inflammatory profile and microbiota in patients with T1D, compared to healthy controls (CTRL) and patients with celiac disease (CD) as gut inflammatory disease controls. Design/Setting/Participants: The inflammatory status and microbiome composition were evaluated in biopsies of the duodenal mucosa of patients with T1D (n=19), CD (n=19) and CTRL (n=16), recruited at San Raffaele Scientific Institute, in Milan, Italy, between 2009 and 2015...
January 19, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323380/sarcophytrols-g-l-novel-minor-metabolic-components-from-south-china-sea-soft-coral-sarcophyton-trocheliophorum-marenzeller
#4
Lin-Fu Liang, Wen-Ting Chen, Ernesto Mollo, Li-Gong Yao, He-Yao Wang, Wei Xiao, Yue-Wei Guo
Minor metabolic components, six new cembranoids sarcophytrols G - L (1 - 6) along with two known related analogues 7 and 8, were isolated from the South China Sea soft coral Sarcophyton trocheliophorum. Their structures were elucidated by extensive spectroscopic analyses (1D- and 2D-NMR, and ESI-MS.) as well as comparison with literature data. As part of our ongoing research project for discovering bioactive substances from Chinese marine invertebrates, compounds 1 - 8 were tested for their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), a key target for the treatment of Type-II diabetes and obesity...
March 21, 2017: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/28322786/adp-ribosylation-factor-like-gtpase-15-enhances-insulin-induced-akt-phosphorylation-in-the-ir-irs1-akt-pathway-by-interacting-with-asap2-and-regulating-pdpk1-activity
#5
Jie Zhao, Min Wang, Wuquan Deng, Daping Zhong, Youzhao Jiang, Yong Liao, Bing Chen, Xiaoli Zhang
Decreased phosphorylation in the insulin signalling pathway is a hallmark of insulin resistance. The causes of this phenomenon are complicated and multifactorial. Recently, genomic analyses have identified ARL15 as a new candidate gene related to diabetes. However, the ARL15 protein function remains unclear. Here, we show that ARL15 is upregulated by insulin stimulation. This effect was impaired in insulin-resistant pathophysiology in TNF-α-treated C2C12 myotubes and in the skeletal muscles of leptin knockout mice...
March 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28319137/the-h3k27-demethylase-utx-regulates-adipogenesis-in-a-differentiation-stage-dependent-manner
#6
Kazushige Ota, Kit I Tong, Kouichiro Goto, Shuta Tomida, Akiyoshi Komuro, Zhong Wang, Kazuto Nishio, Hitoshi Okada
Understanding the molecular mechanisms that drive adipogenesis is important in developing new treatments for obesity and diabetes. Epigenetic regulations determine the capacity of adipogenesis. In this study, we examined the role of a histone H3 lysine 27 demethylase, the ubiquitously transcribed tetratricopeptide repeat protein on the X chromosome (Utx), in the differentiation of mouse embryonic stem cells (mESCs) to adipocytes. Using gene trapping, we examined Utx-deficient male mESCs to determine whether loss of Utx would enhance or inhibit the differentiation of mESCs to adipocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28318634/dna-methyltransferase-1-may-be-a-therapy-target-for-attenuating-diabetic-nephropathy-and-podocyte-injury
#7
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/28314573/decreased-incidence-of-end-stage-renal-disease-in-american-indians-with-diabetes-a-model-for-other-high-risk-populations
#8
Christina M Wyatt
Indigenous populations in North America have very high rates of diabetes and diabetic complications, including end-stage renal disease. A promising new report demonstrates a substantial decline in the incidence of diabetic end-stage renal disease among American Indians and Alaska Natives, coinciding with a public health intervention targeting diabetes management in this population. This success may offer a model for interventions to improve kidney disease outcomes in other high-risk populations.
April 2017: Kidney International
https://www.readbyqxmd.com/read/28306182/barriers-and-enablers-of-type-2-diabetes-self-management-in-people-with-severe-mental-illness
#9
Kathleen Mulligan, Hayley McBain, Frederique Lamontagne-Godwin, Jacqui Chapman, Mark Haddad, Julia Jones, Chris Flood, David Thomas, Alan Simpson
BACKGROUND: People with diabetes and severe mental illness (SMI) experience poorer outcomes than those with diabetes alone. To improve outcomes, it is necessary to understand the difficulties that people with SMI experience in managing their diabetes. AIMS: To identify barriers and enablers to effective diabetes self-management experienced by people with SMI and type 2 diabetes. METHOD: Qualitative methodology using semi-structured interviews was employed...
March 17, 2017: Health Expectations: An International Journal of Public Participation in Health Care and Health Policy
https://www.readbyqxmd.com/read/28304224/evolocumab-and-clinical-outcomes-in-patients-with-cardiovascular-disease
#10
Marc S Sabatine, Robert P Giugliano, Anthony C Keech, Narimon Honarpour, Stephen D Wiviott, Sabina A Murphy, Julia F Kuder, Huei Wang, Thomas Liu, Scott M Wasserman, Peter S Sever, Terje R Pedersen
Background Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain. Methods We conducted a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy...
March 17, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28303255/active-use-of-electronic-health-records-ehrs-and-personal-health-records-phrs-for-epidemiologic-research-sample-representativeness-and-nonresponse-bias-in-a-study-of-women-during-pregnancy
#11
Julie K Bower, Claire E Bollinger, Randi E Foraker, Darryl B Hood, Abigail B Shoben, Albert M Lai
INTRODUCTION: With the growing use of electronic medical records, electronic health records (EHRs), and personal health records (PHRs) for health care delivery, new opportunities have arisen for population health researchers. Our objective was to characterize PHR users and examine sample representativeness and nonresponse bias in a study of pregnant women recruited via the PHR. DESIGN: Demographic characteristics were examined for PHR users and nonusers. Enrolled study participants (responders, n=187) were then compared with nonresponders and a representative sample of the target population...
2017: EGEMS
https://www.readbyqxmd.com/read/28302016/validation-of-tzd-scaffold-as-potential-aris-pharmacophore-modelling-atom-based-3d-qsar-and-docking-studies
#12
Lalita Dahiya, Manoj Kumar Mahapatra, Ramandeep Kaur, Vipin Kumar, Manoj Kumar
Metabolic disorders associated with diabetic patients are a serious concern. Aldose reductase (ALR2) has been identified as first rate-limiting enzyme in the polyol pathway which catalyzes the reduction of glucose to sorbitol. It represents one of the validated targets to develop potential new chemical entities for the prevention and subsequent progression of microvascular diabetic complications. In order to further understand the intricate structural prerequisites of molecules to act as ALR2 inhibitors, ligand-based pharmacophore model, atom-based 3D-QSAR and structure based drug design studies have been performed on a series of 2,4-thiazolidinedione derivatives with ALR2 inhibitory activity...
March 15, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28295962/improving-glycemic-control-in-type-2-diabetes-stimulate-insulin-secretion-or-provide-beta-cell-rest
#13
REVIEW
Daniël H van Raalte, C Bruce Verchere
Type 2 diabetes (T2D) is characterized by a gradual decline of pancreatic beta cell function that determines the progressive course of the disease. While beta-cell failure is an important contributor to hyperglycemia, chronic hyperglycemia itself is also detrimental for beta-cell function, likely by inducing prolonged secretory stress on the beta cell as well as through direct glucotoxic mechanisms that have not been fully defined. For years, research has been carried out in search of therapies targeting hyperglycemia that preserve long-term beta-cell function in T2D, a quest that is still ongoing...
March 14, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28295377/time-restricted-feeding-for-prevention-and-treatment-of-cardiometabolic-disorders
#14
Girish C Melkani, Satchidananda Panda
The soaring prevalence of obesity and diabetes is associated with an increase in comorbidities, including elevated risk for cardiovascular diseases (CVD). CVDs continue to be among the leading causes of death and disability in the United States. While increased nutrition intake from an energy dense diet is known to disrupt metabolic homeostasis and contributes to the disease risk, circadian rhythm disruption is emerging as a new risk factor for CVD. Circadian rhythms coordinate cardiovascular health via temporal control of organismal metabolism and physiology...
March 10, 2017: Journal of Physiology
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
#15
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/28292407/small-bowel-target-devices-and-techniques
#16
REVIEW
Steven A Edmundowicz
The small bowel is a prime target for bariatric and metabolic endoscopic therapies. New insights into the mechanisms of action of surgical therapies have led to new endoscopic therapies for obesity, type 2 diabetes mellitus, and the metabolic syndrome. The development of endoluminal sleeves that bypass the proximal duodenum have replicated some of the effects of surgical bypass procedures. The endoscopic dual-path enteral bypass has created new and treatment options for these conditions. Duodenal mucosal resurfacing offers significant promise for diabetes management...
April 2017: Gastrointestinal Endoscopy Clinics of North America
https://www.readbyqxmd.com/read/28289965/novel-insights-into-the-pathophysiology-and-clinical-aspects-of-diabetic-nephropathy
#17
REVIEW
Zubair Ilyas, Joumana T Chaiban, Armand Krikorian
Diabetic nephropathy (DN) is a well-described complication of diabetes mellitus and the leading cause of end stage renal disease (ESRD). Although increased albuminuria has been the gold standard for screening, data suggests that renal damage starts long before the onset of clinically apparent increases in macro and even micro-albuminuria. Clinical practice guidelines for the prevention of DN have been traditionally focused on the control of serum glucose, blood pressure and dyslipidemia, with some focus on the renin-angiotensin-aldosterone system (RAAS) as a main target for successful therapy...
March 13, 2017: Reviews in Endocrine & Metabolic Disorders
https://www.readbyqxmd.com/read/28285923/design-synthesis-and-structure-activity-relationship-studies-of-novel-free-fatty-acid-receptor-1-agonists-bearing-amide-linker
#18
Jianyong Yang, Zheng Li, Huilan Li, Chunxia Liu, Nasi Wang, Wei Shi, Chen Liao, Xingguang Cai, Wenlong Huang, Hai Qian
The free fatty acid receptor 1 (FFA1/GPR40) has attracted extensive attention as a novel antidiabetic target. Aiming to explore the chemical space of FFA1 agonists, a new series of lead compounds with amide linker were designed and synthesized by combining the scaffolds of NIH screened lead compound 1 and GW9508. Among them, the optimal lead compound 17 exhibited a considerable agonistic activity (45.78%) compared to the NIH screened compound 1 (15.32%). During OGTT in normal mice, the compound 17 revealed a significant glucose-lowering effect (-23...
March 2, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28285098/role-of-leptin-as-a-link-between-metabolism-and-the-immune-system
#19
REVIEW
Antonio Pérez-Pérez, Teresa Vilariño-García, Patricia Fernández-Riejos, Jenifer Martín-González, Juan José Segura-Egea, Víctor Sánchez-Margalet
Leptin is an adipocyte-derived hormone not only with an important role in the central control of energy metabolism, but also with many pleiotropic effects in different physiological systems. One of these peripheral functions of leptin is a regulatory role in the interplay between energy metabolism and the immune system, being a cornerstone of the new field of immunometabolism. Leptin receptor is expressed throughout the immune system and the regulatory effects of leptin include cells from both the innate and adaptive immune system...
March 4, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28283684/pharmacogenetics-in-type-2-diabetes-precision-medicine-or-discovery-tool
#20
REVIEW
Jose C Florez
In recent years, technological and analytical advances have led to an explosion in the discovery of genetic loci associated with type 2 diabetes. However, their ability to improve prediction of disease outcomes beyond standard clinical risk factors has been limited. On the other hand, genetic effects on drug response may be stronger than those commonly seen for disease incidence. Pharmacogenetic findings may aid in identifying new drug targets, elucidate pathophysiology, unravel disease heterogeneity, help prioritise specific genes in regions of genetic association, and contribute to personalised or precision treatment...
March 10, 2017: Diabetologia
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