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Diabetes New Target

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https://www.readbyqxmd.com/read/28549455/inter-act-prevention-of-pregnancy-complications-through-an-e-health-driven-interpregnancy-lifestyle-intervention-study-protocol-of-a-multicentre-randomised-controlled-trial
#1
Annick Bogaerts, Lieveke Ameye, Margriet Bijlholt, Kelly Amuli, Dorine Heynickx, Roland Devlieger
BACKGROUND: Excessive maternal pre-pregnancy and gestational weight gain are related to pregnancy- and birth outcomes. The interpregnancy time window offers a unique opportunity to intervene in order to acquire a healthy lifestyle before the start of a new pregnancy. METHODS: INTER-ACT is an e-health driven multicentre randomised controlled intervention trial targeting women at high risk of pregnancy- and birth related complications. Eligible women are recruited for the study at day 2 or 3 postpartum...
May 26, 2017: BMC Pregnancy and Childbirth
https://www.readbyqxmd.com/read/28548370/current-state-of-a-dual-behavior-of-antimicrobial-peptides-therapeutic-agents-and-promising-delivery-vectors
#2
REVIEW
Urszula Piotrowska, Marcin Sobczak, Ewa Oledzka
Microorganism resistance is an important challenge in modern medicine due to the global uncontrolled use of antibiotics. Natural and synthetic antimicrobial peptides (AMPs) symbolize a new family of antibiotics, which have stimulated research and clinical interest as new therapeutic options for infections. They represent one of the most promising antimicrobial substances, due to their broad spectrum of biological activity, against bacteria, fungi, protozoa, viruses, yeast and even tumour cells. Besides, being antimicrobial, AMPs have been shown to bind and neutralize bacterial endotoxins, as well as possess immunomodulatory, anti-inflammatory, wound-healing, angiogenic and antitumour properties...
May 26, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28547133/hsf1-acetylation-decreases-its-transcriptional-activity-and-enhances-glucolipotoxicity-induced-apoptosis-in-rat-and-human-beta-cells
#3
Indri Purwana, Jun J Liu, Bernard Portha, Jean Buteau
AIMS/HYPOTHESIS: Heat shock factor protein 1 (HSF1) is a transcription factor that regulates the expression of key molecular chaperones, thereby orchestrating the cellular response to stress. This system was recently implicated in the control of insulin sensitivity and is therefore being scrutinised as a novel therapeutic avenue for type 2 diabetes. However, the regulation and biological actions of HSF1 in beta cells remain elusive. Herein, we sought to investigate the regulation of HSF1 in pancreatic beta cells and to study its potential role in cell survival...
May 25, 2017: Diabetologia
https://www.readbyqxmd.com/read/28544782/rationale-and-design-of-amphilimus-sirolimus-eluting-stents-versus-zotarolimus-eluting-stents-in-all-comers-requiring-percutaneous-coronary-intervention-recre8-a-multicenter-randomized-clinical-trial
#4
Rik Rozemeijer, Mèra Stein, Peter Frambach, Michiel Voskuil, Adriaan O Kraaijeveld, Ramón Rodríguez-Olivares, Leo Timmers, Bruno Pereira, Saskia Z Rittersma, Pierfrancesco Agostoni, Pieter A Doevendans, Pieter R Stella
BACKGROUND: Amphilimus sirolimus-eluting stents (A-SES) represent a novel elution technology in the current era of drug-eluting stents with promising results in patients with diabetes mellitus. At present no large trial has been designed to evaluate clinical outcomes of A-SES as compared to new-generation drug-eluting stents in unselected patients. Accordingly, we designed this trial to evaluate clinical noninferiority of A-SES as compared with zotarolimus-eluting stents (ZES) in a real-world, all-comers setting...
May 22, 2017: Catheterization and Cardiovascular Interventions
https://www.readbyqxmd.com/read/28542222/differential-expression-of-islet-glutaredoxin-1-and-5-with-high-reactive-oxygen-species-production-in-a-mouse-model-of-diabesity
#5
Sebastian Friedrich Petry, Fatemeh Sharifpanah, Heinrich Sauer, Thomas Linn
The onset and progression of diabetes mellitus type 2 is highly contingent on the amount of functional beta-cell mass. An underlying cause of beta-cell decay in diabetes is oxidative stress, which markedly affects the insulin producing pancreatic cells due to their poor antioxidant defence capacity. Consequently, disturbances of cellular redox signaling have been implicated to play a major role in beta-cell loss in diabetes mellitus type 2. There is evidence suggesting that the glutaredoxin (Grx) system exerts a protective role for pancreatic islets, but the exact mechanisms have not yet been elucidated...
2017: PloS One
https://www.readbyqxmd.com/read/28542030/predictors-of-poor-clinical-outcomes-after-successful-chronic-total-occlusion-intervention-with-drug-eluting-stents
#6
Gwang-Sil Kim, Byeong-Keuk Kim, Dong-Ho Shin, Jung-Sun Kim, Myeong-Ki Hong, Hyeon-Cheol Gwon, Hyo-Soo Kim, Cheol Woong Yu, Hun Sik Park, In-Ho Chae, Seung-Woon Rha, Yangsoo Jang
BACKGROUND: The aim of this study was to identify the prognostic predictors for the worse clinical outcomes after a successful chronic total occlusion (CTO) intervention with drug-eluting stents. PATIENTS AND RESULTS: A total of 2334 patients in the multicenter Korean CTO registry who underwent a successful CTO intervention with drug-eluting stents (first generation, 1367, new generation, 967) were enrolled. The primary endpoint was the composite of cardiac death, myocardial infarction, and stent thrombosis...
May 24, 2017: Coronary Artery Disease
https://www.readbyqxmd.com/read/28539261/g-protein-coupled-receptor-91-signaling-in-diabetic-retinopathy-and-hypoxic-retinal-diseases
#7
Jianyan Hu, Tingting Li, Xinhua Du, Qiang Wu, Yun-Zheng Le
G protein-coupled receptor 91 (GPR91) is a succinate-specific receptor and activation of GPR91 could initiate a complex signal transduction cascade and upregulate inflammatory and pro-angiogenic cytokines. In the retina, GPR91 is predominately expressed in ganglion cells, a major cellular entity involved in the pathogenesis of diabetic retinopathy (DR) and other hypoxic retinal diseases. During the development of DR and retinopathy of prematurity (ROP), chronic hypoxia causes an increase in the levels of local succinate...
May 21, 2017: Vision Research
https://www.readbyqxmd.com/read/28537398/discovery-of-clinical-candidate-2-2s-6s-2-phenyl-6-hydroxyadamantan-2-yl-1-3-hydroxyazetidin-1-yl-ethanone-bms-816336-an-orally-active-novel-selective-11%C3%AE-hydroxysteroid-dehydrogenase-type-1-inhibitor
#8
Xiang-Yang Ye, Stephanie Y Chen, Shung Wu, David S Yoon, Haixia Wang, Zhenqiu Hong, Stepen P O'Connor, Jun Li, James J Li, Lawrence L Kennedy, Steven J Walker, Akbar Nayeem, Steven Sheriff, Daniel M Camac, Vidyhashankar Ramamurthy, Paul E Morin, Rachel Zebo, Joseph R Taylor, Nathan N Morgan, Randolph P Ponticiello, Thomas Harrity, Atsu Apedo, Rajasree Golla, Ramakrishna Seethala, Mengmeng Wang, Timothy W Harper, Bogdan G Sleczka, Bin He, Mark Kirby, David K Leahy, Jianqing Li, Ronald L Hanson, Zhiwei Guo, Yi-Xin Li, John D DiMarco, Raymond Scaringe, Brad D Maxwell, Frederick Moulin, Joel C Barrish, David A Gordon, Jeffrey A Robl
BMS-816336 (6n-2), a hydroxyl-substituted adamantyl acetamide, has been identified as a novel, potent inhibitor against human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme (IC50 3.0 nM) with >10000 fold selectivity over human 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). BMS-816336 exhibits a robust acute pharmacodynamic effects in cynomolgus monkeys (ED50 0.13 mpk) and in DIO mice. It is orally bioavailable (%F ranges from 20-72% in preclinical species) and has a predicted pharmacokinetic profile of a high peak to trough ratio and short half-life in humans...
May 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28536852/the-role-of-sglt-2-inhibitors-as-part-of-optimal-medical-therapy-in-improving-cardiovascular-outcomes-in-patients-with-diabetes-and-coronary-artery-disease
#9
Wassim Mosleh, Abhinav Sharma, Mandeep S Sidhu, Brian Page, Umesh C Sharma, Michael E Farkouh
The optimal treatment approach to patients with coronary artery disease (CAD), including those with type 2 diabetes mellitus (T2DM), has been extensively evaluated. Several trials of stable ischemic heart disease including patients with T2DM have demonstrated that medical management is comparable to revascularization in terms of mortality and rates of major adverse cardiovascular events (MACE). There has been a growing appreciation for optimal medical therapy's (OMT) role in improving clinical outcomes. It is vital to target T2DM patients to prevent or delay MACE events through advanced OMT, ultimately delaying if not avoiding the need for revascularization...
May 24, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28533296/glp-1r-as-a-target-for-the-treatment-of-diabetic-retinopathy-friend-or-foe
#10
Rafael Simó, Cristina Hernández
Glucagon-like peptide 1 receptor (GLP-1R) agonists are increasingly being used as treatment for type 2 diabetes. Since the U.S. Food and Drug Administration published recommendations about the cardiovascular safety of new antidiabetes therapies for treating type 2 diabetes in 2008, the results of two outstanding clinical trials using GLP-1R agonists addressing this issue (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results-A Long Term Evaluation [LEADER] and Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes [SUSTAIN-6]) have been published...
June 2017: Diabetes
https://www.readbyqxmd.com/read/28533219/obesity-linked-phosphorylation-of-sirt1-by-ck2-inhibits-its-nuclear-localization-and-promotes-fatty-liver
#11
Sung E Choi, Sanghoon Kwon, Sunmi Seok, Zhen Xiao, Kwan-Woo Lee, Yup Kang, Xiaoling Li, Kosaku Shinoda, Shingo Kajimura, Byron Kemper, Jongsook Kim Kemper
Sirtuin1 (SIRT1) deacetylase delays and improves many obesity-related diseases, including non-alcoholic fatty liver disease (NAFLD) and diabetes, and has received great attention as a drug target. SIRT1 function is aberrantly low in obesity, so understanding the underlying mechanisms is important for drug development. Here, we show that obesity-linked phosphorylation of SIRT1 inhibits its function and promotes pathological symptoms of NAFLD. In proteomic analysis, Ser-164 was identified as a major serine phosphorylation site in SIRT1 in obese, but not lean, mice, and this phosphorylation was catalyzed by casein kinase-2 (CK2), the levels of which were dramatically elevated in obesity...
May 22, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28530546/the-role-of-qsar-and-virtual-screening-studies-in-type-2-diabetes-drug-discovery
#12
Simone Q Pantaleão, Drielli G V Fujji, Vinícius G Maltarollo, Danielle da C Silva, Gustavo H G Trossini, Karen C Weber, Luis P B Scott, Kathia M Honorio
BACKGROUND: Due to the increasing number of diabetes cases worldwide, there is an international concern to provide even more effective treatments to control this condition. METHODS: This review brings together a selection of studies that helped to broaden the comprehension of various biological targets and associated mechanisms involved in type 2 diabetes mellitus. RESULTS: Such studies demonstrated that QSAR techniques and virtual screenings have been successfully employed in drug design projects...
May 22, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28529958/spatiotemporal-regulators-for-insulin-stimulated-glut4-vesicle-exocytosis
#13
REVIEW
Xiaoxu Zhou, Ping Shentu, Yingke Xu
Insulin increases glucose uptake and storage in muscle and adipose cells, which is accomplished through the mobilization of intracellular GLUT4 storage vesicles (GSVs) to the cell surface upon stimulation. Importantly, the dysfunction of insulin-regulated GLUT4 trafficking is strongly linked with peripheral insulin resistance and type 2 diabetes in human. The insulin signaling pathway, key signaling molecules involved, and precise trafficking itinerary of GSVs are largely identified. Understanding the interaction between insulin signaling molecules and key regulatory proteins that are involved in spatiotemporal regulation of GLUT4 vesicle exocytosis is of great importance to explain the pathogenesis of diabetes and may provide new potential therapeutic targets...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28529157/protective-treatments-and-their-target-retinal-ganglion-cells-in-diabetic-retinopathy
#14
REVIEW
Jing Zhang, Rong Liu, Hong-Yu Kuang, Xin-Yuan Gao, Hao-Ling Liu
Diabetic retinopathy(DR)is one of the complications of diabetes which could cause severe vision loss. Retinal ganglion cell(RGC)injury has been confirmed prior to micro-vascular damage. Over the past few decades, a number of animal and clinical studies have confirmed that RGC impairment leads to an early deterioration of vision in DR. Inhibition of aldose reductase (AR), advanced glycation end product (AGE), oxidative stress, glutamate toxicity, and an inflammatory response may play important roles in protecting RGCs in DR...
May 18, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28528078/change-in-hemoglobin-a1c-one-year-following-the-2014-american-diabetes-association-guideline-update
#15
G Todd Alonso, Laura Pyle, Brigitte Frohnert
AIMS: In June 2014, the American Diabetes Association lowered recommended hemoglobin A1c (HbA1c) targets from <8.5% (69mmol/mol) for children <6years of age and from <8.0% (64mmol/mol) for children 6-12years of age to <7.5% (58mmol/mol). Lower target HbA1c may lead to better glycemic control but could increase the risk of severe hypoglycemia. METHODS: Patients with type 1 diabetes >1year duration, age 0-12years and seen in our center between January 1 and June 30, 2014 or between January 1 and June 30, 2015 were included...
May 10, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28528075/adopting-the-new-world-health-organization-diagnostic-criteria-for-gestational-diabetes-how-the-prevalence-changes-in-a-high-risk-region-in-australia
#16
Vincent W Wong, Andrew Lin, Hamish Russell
AIMS: In this study, we assessed changes in prevalence of gestational diabetes mellitus (GDM) in a region with diverse cultural backgrounds in Australia under the new World Health Organization (WHO) diagnostic criteria, with reference to the woman's ethnicity, age and pre-pregnant body mass index (BMI). METHODS: We recorded results of all 75-gram oral glucose tolerance tests (OGTTs) performed on pregnant women between February and December 2015 together with their demographic details, and determined the prevalence of GDM based on the old Australian Diabetes in Pregnancy Society (ADIPS) and the new WHO criteria respectively...
April 25, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28526540/sodium-dependent-glucose-transporters-sglt-in-human-ischemic-heart-a-new-potential-pharmacological-target
#17
Alessandra Di Franco, Giulia Cantini, Alessia Tani, Raffaele Coppini, Sandra Zecchi-Orlandini, Laura Raimondi, Michaela Luconi, Edoardo Mannucci
BACKGROUND: Empagliflozin is reported to reduce cardiovascular mortality and the rate of hospitalization for heart failure in type 2 diabetic patients with prior cardiovascular events. The mechanisms underlying the cardiac effects of this sodium/glucose transporter 2 (SGT2) inhibitor have not yet been clarified, though a direct action of the drug on the cardiomyocytes could be hypothesized. The aim of the present study is to assess the relative expression of SGLT2 and SGLT1, the two most relevant members of the SGLT family being potentially responsive to empagliflozin, in normal, ischemic and hypertrophic human hearts...
May 9, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28525563/omics-biomarkers-in-ophthalmology
#18
Susette Lauwen, Eiko K de Jong, Dirk J Lefeber, Anneke I den Hollander
"Omics" refers to high-throughput analyses of genes, proteins, or metabolites in a biological system, and is increasingly used for ophthalmic research. These system-based approaches can unravel disease-related processes and are valuable for biomarker discovery. Furthermore, potential therapeutic targets can be identified based on omics results, and targeted follow-up experiments can be designed to gain molecular understanding of the disease and to test new therapies. Here, we review the application of omics techniques in eye diseases, focusing on age-related macular degeneration (AMD), diabetic retinopathy (DR), retinal detachment (RD), myopia, glaucoma, Fuchs' corneal dystrophy (FCD), cataract, keratoconus, and dry eyes...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28524168/endocrine-disrupting-chemicals-and-the-regulation-of-energy-balance
#19
REVIEW
Angel Nadal, Ivan Quesada, Eva Tudurí, Rubén Nogueiras, Paloma Alonso-Magdalena
Energy balance involves the adjustment of food intake, energy expenditure and body fat reserves through homeostatic pathways. These pathways include a multitude of biochemical reactions, as well as hormonal cues. Dysfunction of this homeostatic control system results in common metabolism-related pathologies, which include obesity and type 2 diabetes mellitus. Metabolism-disrupting chemicals (MDCs) are a particular class of endocrine-disrupting chemicals that affect energy homeostasis. MDCs affect multiple endocrine mechanisms and thus different cell types that are implicated in metabolic control...
May 19, 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/28522654/diabetic-kidney-disease-challenges-progress-and-possibilities
#20
Radica Z Alicic, Michele T Rooney, Katherine R Tuttle
Diabetic kidney disease develops in approximately 40% of patients who are diabetic and is the leading cause of CKD worldwide. Although ESRD may be the most recognizable consequence of diabetic kidney disease, the majority of patients actually die from cardiovascular diseases and infections before needing kidney replacement therapy. The natural history of diabetic kidney disease includes glomerular hyperfiltration, progressive albuminuria, declining GFR, and ultimately, ESRD. Metabolic changes associated with diabetes lead to glomerular hypertrophy, glomerulosclerosis, and tubulointerstitial inflammation and fibrosis...
May 18, 2017: Clinical Journal of the American Society of Nephrology: CJASN
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