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Diabetes New Target

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https://www.readbyqxmd.com/read/28815013/diabetic-retinopathy-reversibility-of-epigenetic-modifications-and-new-therapeutic-targets
#1
REVIEW
Xinyuan Zhang, Lin Zhao, Brett Hambly, Shisan Bao, Kaiyue Wang
In recent years, considerable progress has been made in the molecular mechanisms of epigenetics in disease development and progression, the reversible characteristics of epigenetic modification provide new insights for the treatment of such diseases. The pathogenesis of diabetic retinopathy (DR) has not yet been fully understood, treatment of refractory and recurrent diabetic macular edema remains a big change in clinical practice. This review emphasizes that reversibility of epigenetic modification could provide a new strategy for the prevention and treatment of diseases...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28810642/overexpressed-enos-upregulates-sirt1-expression-and-protects-mouse-pancreatic-%C3%AE-cells-from-apoptosis
#2
Tingting Hu, Ye Chen, Qian Jiang, Jun Lin, Hewei Li, Ping Wang, Leping Feng
Loss of sirtuin 1 (SIRT1) activity may be associated with metabolic diseases, including diabetes. The aim of the present study was to investigate the potential effects of overexpressed endothelial nitric oxide synthase (eNOS) on cell proliferation and apoptosis with SIRT1 activation in the Min6 mouse pancreatic β cell line. A pcDNA3.0-eNOS plasmid was constructed and transfected into Min6 cells for 24 h prior to harvesting. eNOS expression was validated and SIRT1 expression was detected following plasmid transfection using reverse transcription-quantitative polymerase chain reaction and western blot analysis, which demonstrated that the expression levels of eNOS and SIRT1 were significantly upregulated...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810126/combined-virtual-screening-and-substructure-search-for-discovery-of-novel-fabp4-inhibitors
#3
Haiyan Cai, Ting Wang, Zhuo Yang, Zhijian Xu, Guimin Wang, Heyao Wang, Weiliang Zhu, Kaixian Chen
Fatty acid-binding protein 4 (FABP4, AFABP) is a potential drug target for diabetes and atherosclerosis. In this study, a series of novel FABP4 inhibitors were discovered through combining virtual screening and substructure search. Seventeen compounds exhibited FABP4 inhibitory activities with IC50 <10 μM, among which eleven compounds showed high selectivity against FABP3. The best compound 36b displayed an IC50 value of 1.5 μM. Molecular docking and point mutation studies revealed that Gln95, Arg126 and Tyr128 play key roles for these compounds binding with FABP4...
August 15, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28807156/metabolic-factors-and-adult-neurogenesis-impacts-of-chinese-herbal-medicine-on-brain-repair-in-neurological-diseases
#4
Chong Gao, Jiangang Shen
Adult neurogenesis plays the important roles in animal cognitive and emotional behaviors. Abnormal proliferation and differentiation of neural stem cells (NSCs) usually associate with the neural dysfunctions induced by different brain disorders. Therefore, targeting neurogenic factors could be a promoting strategy for neural regeneration and brain repair. Importantly, epidemiological studies suggest metabolism disorders like diabetes and obesity significantly increase the risk of neurological and psychiatric diseases...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28805979/effects-of-mtor-inhibition-on-cardiac-and-adipose-tissue-pathology-and-glucose-metabolism-in-rats-with-metabolic-syndrome
#5
Ayako Uchinaka, Mamoru Yoneda, Yuichiro Yamada, Toyoaki Murohara, Kohzo Nagata
The mammalian target of rapamycin (mTOR) is a regulator of metabolism and is implicated in pathological conditions such as obesity and diabetes. We aimed to investigate the role of mTOR in obesity. A new animal model of metabolic syndrome (MetS), named DahlS.Z-Lepr(fa) /Lepr(fa) (DS/obese) rats was established previously in our laboratory. In this study, we used this model to evaluate the effects of mTOR inhibition on cardiac and adipose tissue pathology and glucose metabolism. DS/obese rats were treated with the mTOR inhibitor, everolimus, (0...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28805970/a-novel-free-fatty-acid-receptor-1-gpr40-ffar1-agonist-mr1704-enhances-glucose-dependent-insulin-secretion-and-improves-glucose-homeostasis-in-rats
#6
Naoto Tsuda, Atsuko Kawaji, Toshihiro Sato, Mitsuhiro Takagi, Chika Higashi, Yutaka Kato, Kumiko Ogawa, Hiroyasu Naba, Munetaka Ohkouchi, Masaki Nakamura, Yoshitaka Hosaka, Junichi Sakaki
Activation of G protein-coupled receptor 40/Free fatty acid receptor 1 (GPR40/FFAR1), which is highly expressed in pancreatic β cells, is considered an important pharmacologic target for the treatment of type 2 diabetes mellitus. The aim of this study was to determine the effect of MR1704, a novel GPR40/FFAR1 agonist, on glucose homeostasis in rats. MR1704 is a highly potent and selective, orally bioavailable agonist with similar in vitro potencies among humans, mice, and rats. Treatment of rat islets with MR1704 increased glucose-dependent insulin secretion...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28804275/metabolomics-based-markers-predict-type-2-diabetes-in-a-14-year-follow-up-study
#7
Jun Liu, Sabina Semiz, Sven J van der Lee, Ashley van der Spek, Aswin Verhoeven, Jan B van Klinken, Eric Sijbrands, Amy C Harms, Thomas Hankemeier, Ko Willems van Dijk, Cornelia M van Duijn, Ayşe Demirkan
BACKGROUND: The growing field of metabolomics has opened up new opportunities for prediction of type 2 diabetes (T2D) going beyond the classical biochemistry assays. OBJECTIVES: We aimed to identify markers from different pathways which represent early metabolic changes and test their predictive performance for T2D, as compared to the performance of traditional risk factors (TRF). METHODS: We analyzed 2776 participants from the Erasmus Rucphen Family study from which 1571 disease free individuals were followed up to 14-years...
2017: Metabolomics: Official Journal of the Metabolomic Society
https://www.readbyqxmd.com/read/28803820/titration-a-randomized-study-to-assess-2-treatment-algorithms-with-new-insulin-glargine-300-units-ml
#8
Jean-François Yale, Lori Berard, Mélanie Groleau, Pasha Javadi, John Stewart, Stewart B Harris
OBJECTIVE: It was uncertain whether an algorithm that involves increasing insulin dosages by 1 unit/day may cause more hypoglycemia with the longer-acting insulin glargine 300 units/mL (GLA-300). The objective of this study was to compare safety and efficacy of 2 titration algorithms, INSIGHT and EDITION, for GLA-300 in people with uncontrolled type 2 diabetes mellitus, mainly in a primary care setting. METHODS: This was a 12-week, open-label, randomized, multicentre pilot study...
August 10, 2017: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/28803690/new-insights-into-non-conventional-epitopes-as-t-cell-targets-the-missing-link-for-breaking-immune-tolerance-in-autoimmune-disease
#9
REVIEW
James Harbige, Martin Eichmann, Mark Peakman
The mechanism by which immune tolerance is breached in autoimmune disease is poorly understood. One possibility is that post-translational modification of self-antigens leads to peripheral recognition of neo-epitopes against which central and peripheral tolerance is inadequate. Accumulating evidence points to multiple mechanisms through which non-germline encoded sequences can give rise to these non-conventional epitopes which in turn engage the immune system as T cell targets. In particular, where these modifications alter the rules of epitope engagement with MHC molecules, such non-conventional epitopes offer a persuasive explanation for associations between specific HLA alleles and autoimmune diseases...
August 10, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28801099/immediate-reduction-of-serum-citrulline-but-no-change-of-steroid-profile-after-initiation-of-metformin-in-individuals-with-type-2-diabetes
#10
Michaela Breier, Simone Wahl, Cornelia Prehn, Uta Ferrari, Vanessa Sacco, Michaela Weise, Harald Grallert, Jerzy Adamski, Andreas Lechner
Metformin is the most important first-line treatment for type 2 diabetes mellitus (T2DM) but its exact mode of action remains unknown. In this study, we used targeted metabolomics to gain new insights into the metabolic effects of metformin in humans with T2DM. We also examined changes in the serum steroid hormone profile. We quantified 167 serum metabolites and 19 steroid hormones using liquid chromatography-tandem mass spectrometry at three time points in individuals with previously untreated T2DM: before the start of metformin therapy (time point A), after the first dose (B) and after short-term therapy for 4-6 weeks (C)...
August 8, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28797256/selenoprotein-s-a-therapeutic-target-for-diabetes-and-macroangiopathy
#11
REVIEW
Shan-Shan Yu, Jian-Ling Du
Inflammatory response, oxidative stress, and endoplasmic reticulum (ER) stress are important pathophysiological bases of the occurrence and development of diabetes mellitus (DM) and macroangiopathy complications. Selenoprotein S (SELENOS) is involved in the regulation of these mechanisms; therefore, its association with DM and macroangiopathy has gradually received attention from scholars worldwide. SELENOS has different biological functions in different tissues and organs: it exerts antioxidant protection and has anti-ER stress effects in the pancreas and blood vessels, while it promotes the occurrence and development of insulin resistance in the liver, adipose tissue, and skeletal muscle...
August 10, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28795381/research-progress-on-prevention-and-treatment-of-glucolipid-metabolic-disease-with-integrated-traditional-chinese-and-western-medicine
#12
Jiao Guo
Hyperlipidemia, type 2 diabetes mellitus, nonalcoholic fatty liver and many other metabolic disorder are frequently co-existing in patients. In addition, these diseases are closely related in pathophysiological settings. However, increasing of the disease incidence, lacking of comprehensive prevention and control measurements against the key pathology point concomitant occurrence with the pattern of the single disease, single target therapy, that is leading therapeutic strategy for these metabolic disorders in the setting of Western medicine (WM)...
June 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28794211/dietary-whole-egg-consumption-attenuates-body-weight-gain-and-is-more-effective-than-supplemental-cholecalciferol-in-maintaining-vitamin-d-balance-in-type-2-diabetic-rats
#13
Cassondra J Saande, Samantha K Jones, Kaylee E Hahn, Carter H Reed, Matthew J Rowling, Kevin L Schalinske
Background: Type 2 diabetes (T2D) is characterized by vitamin D insufficiency owing to excessive urinary loss of 25-hydroxycholecalciferol [25(OH)D]. We previously reported that a diet containing dried whole egg, a rich source of vitamin D, was effective at maintaining circulating 25(OH)D concentrations in rats with T2D. Furthermore, whole egg consumption reduced body weight gain in rats with T2D.Objective: This study was conducted to compare whole egg consumption with supplemental cholecalciferol with respect to vitamin D balance, weight gain, and body composition in rats with T2D...
August 9, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28791309/research-progress-on-mechanism-of-podocyte-depletion-in-diabetic-nephropathy
#14
REVIEW
Haoran Dai, Qingquan Liu, Baoli Liu
Diabetic nephropathy (DN) together with glomerular hyperfiltration has been implicated in the development of diabetic microangiopathy in the initial stage of diabetic diseases. Increased amounts of urinary protein in DN may be associated with functional and morphological alterations of podocyte, mainly including podocyte hypertrophy, epithelial-mesenchymal transdifferentiation (EMT), podocyte detachment, and podocyte apoptosis. Accumulating studies have revealed that disruption in multiple renal signaling pathways had been critical in the progression of these pathological damages, such as adenosine monophosphate-activated kinase signaling pathways (AMPK), wnt/β-catenin signaling pathways, endoplasmic reticulum stress-related signaling pathways, mammalian target of rapamycin (mTOR)/autophagy pathway, and Rho GTPases...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28782293/systematic-review-of-publicity-interventions-to-increase-awareness-amongst-healthcare-professionals-and-the-public-to-promote-earlier-diagnosis-of-type-1-diabetes-in-children-and-young-people
#15
R Deylami, J Townson, M Mann, J W Gregory
BACKGROUND: Children with new onset type 1 diabetes (T1D) are at risk of developing the life-threatening condition ketoacidosis if they have a delayed diagnosis. The rate of children presenting in ketoacidosis remains high in a number of countries worldwide. To ensure interventions to raise awareness of symptoms are effective a systematic review was conducted to evaluate previous publicity campaigns. METHODS: A range of databases was searched using search terms relating to T1D, publicity campaigns, and symptom awareness...
August 7, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28776320/cost-effectiveness-of-support-for-people-starting-a-new-medication-for-a-long-term-condition-through-community-pharmacies-an-economic-evaluation-of-the-new-medicine-service-nms-compared-with-normal-practice
#16
Rachel A Elliott, Lukasz Tanajewski, Georgios Gkountouras, Anthony J Avery, Nick Barber, Rajnikant Mehta, Matthew J Boyd, Asam Latif, Antony Chuter, Justin Waring
BACKGROUND: The English community pharmacy New Medicine Service (NMS) significantly increases patient adherence to medicines, compared with normal practice. We examined the cost effectiveness of NMS compared with normal practice by combining adherence improvement and intervention costs with the effect of increased adherence on patient outcomes and healthcare costs. METHODS: We developed Markov models for diseases targeted by the NMS (hypertension, type 2 diabetes mellitus, chronic obstructive pulmonary disease, asthma and antiplatelet regimens) to assess the impact of patients' non-adherence...
August 3, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/28770326/the-effects-of-metformin-on-gut-microbiota-and-the-immune-system-as-research-frontiers
#17
REVIEW
Michael Pollak
Recent studies have revealed that metformin influences gut microbiota and the immune system although neither is a classic target of the drug. This research has revealed complexity not previously appreciated, and opened new research directions. The extent to which immunomodulatory effects and actions on the microbiota are related to each other and account for effects on host energy metabolism remains to be determined. These sites of action may be relevant not only to the efficacy of metformin for its established use in type 2 diabetes, but also to proposed novel indications in oncology and other diseases...
August 2, 2017: Diabetologia
https://www.readbyqxmd.com/read/28770317/mitochondrial-h-atp-synthase-in-human-skeletal-muscle-contribution-to-dyslipidaemia-and-insulin-resistance
#18
Laura Formentini, Alexander J Ryan, Manuel Gálvez-Santisteban, Leslie Carter, Pam Taub, John D Lapek, David J Gonzalez, Francisco Villarreal, Theodore P Ciaraldi, José M Cuezva, Robert R Henry
AIMS/HYPOTHESIS: Mitochondria are important regulators of the metabolic phenotype in type 2 diabetes. A key factor in mitochondrial physiology is the H(+)-ATP synthase. The expression and activity of its physiological inhibitor, ATPase inhibitory factor 1 (IF1), controls tissue homeostasis, metabolic reprogramming and signalling. We aimed to characterise the putative role of IF1 in mediating skeletal muscle metabolism in obesity and diabetes. METHODS: We examined the 'mitochondrial signature' of obesity and type 2 diabetes in a cohort of 100 metabolically characterised human skeletal muscle biopsy samples...
August 2, 2017: Diabetologia
https://www.readbyqxmd.com/read/28770170/high-throughput-microplate-based-assay-to-monitor-plasma-membrane-wounding-and-repair
#19
Sarika Pathak-Sharma, Xiaoli Zhang, Jonathan G T Lam, Noah Weisleder, Stephanie M Seveau
The plasma membrane of mammalian cells is susceptible to disruption by mechanical and biochemical damages that frequently occur within tissues. Therefore, efficient and rapid repair of the plasma membrane is essential for maintaining cellular homeostasis and survival. Excessive damage of the plasma membrane and defects in its repair are associated with pathological conditions such as infections, muscular dystrophy, heart failure, diabetes, and lung and neurodegenerative diseases. The molecular events that remodel the plasma membrane during its repair remain poorly understood...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28769873/targeting-obesity-and-diabetes-to-treat-heart-failure-with-preserved-ejection-fraction
#20
REVIEW
Raffaele Altara, Mauro Giordano, Einar S Nordén, Alessandro Cataliotti, Mazen Kurdi, Saeed N Bajestani, George W Booz
Heart failure with preserved ejection fraction (HFpEF) is a major unmet medical need that is characterized by the presence of multiple cardiovascular and non-cardiovascular comorbidities. Foremost among these comorbidities are obesity and diabetes, which are not only risk factors for the development of HFpEF, but worsen symptoms and outcome. Coronary microvascular inflammation with endothelial dysfunction is a common denominator among HFpEF, obesity, and diabetes that likely explains at least in part the etiology of HFpEF and its synergistic relationship with obesity and diabetes...
2017: Frontiers in Endocrinology
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