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Diabetes New Target

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https://www.readbyqxmd.com/read/28635658/asperentin-b-a-new-inhibitor-of-the-protein-tyrosine-phosphatase-1b
#1
Jutta Wiese, Hülya Aldemir, Rolf Schmaljohann, Tobias A M Gulder, Johannes F Imhoff
In the frame of studies on secondary metabolites produced by fungi from deep-sea environments we have investigated inhibitors of enzymes playing key roles in signaling cascades of biochemical pathways relevant for the treatment of diseases. Here we report on a new inhibitor of the human protein tyrosine phosphatase 1B (PTP1B), a target in the signaling pathway of insulin. A new asperentin analog is produced by an Aspergillussydowii strain isolated from the sediment of the deep Mediterranean Sea. Asperentin B (1) contains an additional phenolic hydroxy function at C-6 and exhibits an IC50 value against PTP1B of 2 μM in vitro, which is six times stronger than the positive control, suramin...
June 21, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28635648/deoxyelephantopin-and-isodeoxyelephantopin-as-potential-anticancer-agents-with-effects-on-multiple-signaling-pathways
#2
REVIEW
Tahir Mehmood, Amara Maryam, Hamed A Ghramh, Muhammad Khan, Tonghui Ma
Cancer is the 2nd leading cause of death worldwide. The development of drugs to target only one specific signaling pathway has limited therapeutic success. Developing chemotherapeutics to target multiple signaling pathways has emerged as a new prototype for cancer treatment. Deoxyelephantopin (DET) and isodeoxyelephantopin (IDET) are sesquiterpene lactone components of "Elephantopus scaber and Elephantopus carolinianus", traditional Chinese medicinal herbs that have long been used as folk medicines to treat liver diseases, diabetes, diuresis, bronchitis, fever, diarrhea, dysentery, cancer, and inflammation...
June 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28629533/design-of-new-traditional-chinese-medicine-herbal-formulae-for-treatment-of-type-2-diabetes-mellitus-based-on-network-pharmacology
#3
Rui-Feng Hu, Xiao-Bo Sun
In the present study, 28 Chinese medicinal herbs belonging to traditional Chinese medicine (TCM) for the treatment of type 2 diabetes were selected to explore the application of network pharmacology in developing new Chinese herbal medicine formulae for the treatment of type 2 diabetes mellitus (T2DM). These herbs have the highest appearance rate in the literature, and their compounds are listed. The human protein-protein interaction network and the T2DM disease protein interaction network were constructed...
June 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/28627773/oleanolic-acid-derivative-dks26-exerts-antidiabetic-and-hepatoprotective-effects-in-diabetic-mice-and-promotes-glp-1-secretion-and-expression-in-intestinal-cells
#4
Fei-Fei Chen, Jian-Ta Wang, Li-Xia Zhang, Shu-Fang Xing, Yun-Xia Wang, Kai Wang, Shu-Li Deng, Ji-Quan Zhang, Lei Tang, Hao-Shu Wu
BACKGROUND AND PURPOSE: Glucagon-like peptide-1 (GLP-1) is an important target for diabetes therapy based on its key role in maintaining glucose and lipid homeostasis. This study was designed to investigate antidiabetic and hepatoprotective effects of novel oleanolic acid derivative DKS26 in diabetic mice and elucidate its underlying GLP-1 related antidiabetic mechanisms in vitro and in vivo. EXPERIMENTAL APPROACH: The therapeutic effects of DKS26 were inspected in streptozotocin (STZ)-induced and db/db diabetic mouse models including levels of plasma glucose, glycosylated serum protein (GSP), lipid profiles, insulin, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), oral glucose tolerance (OGT), pancreatic islets and hepatic histopathological morphology, liver lipid levels and expression of pro-inflammation cytokines...
June 19, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28623668/impact-of-pci-appropriateness-in-the-long-term-outcomes-of-consecutive-patients-treated-with-second-generation-drug-eluting-stents
#5
Ana Cristina Seixas, Amanda Sousa, Jose de Ribamar Costa, Adriana Costa Moreira, Ricardo Costa, Lucas Damiani, Cantídio Campos Neto, Galo Maldonado, Manuel Cano, J Eduardo Sousa
BACKGROUND: Appropriate use criteria (AUC) for coronary revascularization were developed to deliver high-quality care; however, the prognostic impact of these criteria remains unclear. We sought to assess the outcomes of patients treated with second-generation drug-eluting stent (DES) classified according to the updated American College of Cardiology Foundation/American Heart Association/Society for Cardiac Angiography and Intervention AUC for percutaneous coronary intervention (PCI)...
June 15, 2017: Journal of Invasive Cardiology
https://www.readbyqxmd.com/read/28620646/kidney-transplant-recipients-perspectives-on-cardiovascular-disease-and-related-risk-factors-after-transplantation-a-qualitative-study
#6
Fabián Ballesteros, Julie Allard, Céline Durand, Héloïse Cardinal, Lyne Lalonde, Marie-Chantal Fortin
BACKGROUND: Cardiovascular disease (CVD) is a major cause of mortality among kidney transplant recipients (KTRs). These patients have a high prevalence of risk factors, such as hypertension, diabetes, and dyslipidemia. Despite regular medical care, few of them reach the recommended therapeutic targets. The objective of this study is to describe KTRs' perspectives on CVD and related risk factors, as well as their priorities for posttransplant care. METHODS: Twenty-six KTRs participated in a semistructured interview about their personal experience and offered their perspectives on CVD risk factors posttransplant...
June 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28620094/an-interrupted-time-series-analysis-to-determine-the-effect-of-an-electronic-health-record-based-intervention-on-appropriate-screening-for-type-2-diabetes-in-urban-primary-care-clinics-in-new-york-city
#7
Jeanine B Albu, Nancy Sohler, Rui Li, Xuan Li, Edwin Young, Edward W Gregg, Dennis Ross-Degnan
OBJECTIVE: To determine the impact of a health system-wide primary care diabetes management system, which included targeted guidelines for type 2 diabetes (T2DM) and prediabetes (dysglycemia) screening, on detection of previously undiagnosed dysglycemia cases. RESEARCH DESIGN AND METHODS: Intervention included electronic health record (EHR)-based decision support and standardized providers and staff training for using the American Diabetes Association guidelines for dysglycemia screening...
June 15, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28618903/planning-secondary-prevention-room-for-improvement
#8
Alejandro Cortés-Beringola, Donna Fitzsimons, Antonio Pelliccia, Guillermo Moreno, Roberto Martín-Asenjo, Héctor Bueno
The prognosis of patients after acute coronary syndromes is still suboptimal, mainly due to the risk of recurrent adverse coronary events, which is greatest during the first year, but persists over one's lifetime. Meaningful progress in preventing cardiovascular events has been achieved. However, there remains much room for improvement by embracing innovative therapies and investing in multidisciplinary approaches. Pharmacological interventions focused on optimising antithrombotic and lipid-lowering therapies are both pillars of secondary prevention that have seen recent ground-breaking advances...
June 2017: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/28615513/thioredoxin-plays-a-key-role-in-retinal-neuropathy-prior-to-endothelial-damage-in-diabetic-mice
#9
Xiang Ren, Chen Li, Junli Liu, Chenghong Zhang, Yuzhen Fu, Nina Wang, Haiying Ma, Heyuan Lu, Hui Kong, Li Kong
Diabetes is a chronic metabolic syndrome that results in changes in carbohydrate, lipid and protein metabolism. With diabetes for a long time, it increases the risk of diabetic retinopathy (DR) and long-term morbidity and mortality. Moreover, emerging evidence suggests that neuron damage occurs earlier than microvascular complications in DR patients, but the underlying mechanism is unclear. We investigated diabetes-induced retinal neuropathy and elucidated key molecular events to identify new therapeutic targets for the clinical treatment and prevention of DR...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28613014/raising-the-list-of-sirt7-targets-to-a-new-level
#10
Nicolas G Simonet, Alejandro Vaquero
Sirtuins are crucial proteins involved in sensing and coordinating the response to different forms of stress, mainly through NAD(+) -dependent deacetylation of proteins. For that reason, sirtuins are directly involved in many human pathologies including cancer, diabetes, cardiovascular and neurodegenerative diseases. SirT7, one of the less well-understood sirtuins, has been associated with ribosome biogenesis, gene expression, metabolism and cancer. Despite the wide range of these functions, only a handful of targets for SirT7 have so far been described...
June 14, 2017: Proteomics
https://www.readbyqxmd.com/read/28610911/airway-glucose-homeostasis-a-new-target-in-the-prevention-and-treatment-of-pulmonary-infection
#11
REVIEW
Emma H Baker, Deborah L Baines
In health, the glucose concentration of airway surface liquid (ASL) is 0.4mM, around 12 times lower than blood glucose concentration. Airway glucose homeostasis is a set of processes that actively maintain low ASL glucose concentration against the transepithelial gradient. Tight junctions between airway epithelial cells restrict paracellular glucose movement. Epithelial cellular glucose transport and metabolism removes glucose from ASL. Low ASL glucose concentrations make an important contribution to airways defence against infection, limiting bacterial growth by restricting nutrient availability...
June 10, 2017: Chest
https://www.readbyqxmd.com/read/28609824/12-lipoxygenase-inhibitor-improves-functions-of-cytokine-treated-human-islets-and-type-2-diabetic-islets
#12
Kaiwen Ma, So Hyun Park, Glenn Lindsey, Jackson Laura, Barot Tatvam, Jessica R Weaver, David A Taylor-Fishwick, Diane K Luci, David J Maloney, Raghavendra G Mirmira, Yumi Imai, Jerry L Nadler
Context: 12-lipoxygenase (12-LO) pathway produces pro-inflammatory metabolites and its activation is implicated in islet inflammation associated with type 1 and type 2 diabetes (T1D, T2D). Objectives: We aimed to test the efficacy of ML355, a new highly selective small molecule inhibitor of 12-LO, for the preservation of islet function. Design: Human islets from non-diabetic donors were incubated with the mixture of TNFα, interluekin-1β, and interferon-γ to model islet inflammation...
May 10, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28606929/targeting-oxygen-sensing-prolyl-hydroxylase-phd-for-metformin-associated-lactic-acidosis-treatment
#13
Tomoko Oyaizu-Toramaru, Tomohiro Suhara, Noriyo Hayakawa, Takashi Nakamura, Akiko Kubo, Shizuka Minamishima, Kyoji Yamaguchi, Takako Hishiki, Hiroshi Morisaki, Makoto Suematsu, Yoji Andrew Minamishima
Metformin is one of the most widely used therapeutics for type 2 diabetes mellitus and also has anti-cancer and anti-aging properties. However, it is known to induce metformin-associated lactic acidosis (MALA), a severe medical condition with poor prognosis, especially in individuals with renal dysfunction. Inhibition of prolyl hydroxylase (PHD) is known to activate transcription factor HIF (hypoxia-inducible factor) that increases lactate efflux as a result of enhanced glycolysis, but it also enhances gluconeogenesis from lactate in the liver that contributes to reducing circulating lactate levels...
June 12, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28605974/hplc-method-for-measurement-of-human-salivary-%C3%AE-amylase-inhibition-by-aqueous-plant-extracts
#14
István Takács, Ákos Takács, Anikó Pósa, Gyöngyi Gyémánt
Control of hyperglycemia is an important treatment in metabolic disorders such as type II diabetes and obesity. α-Amylase, as the first enzyme of glucose release from dietary polysaccharides, is a potential target to identify new sources of novel anti-obesity and anti-diabetic drugs. In this work, different herbal extracts as α-amylase inhibitors were studied by measuring the rate of the cleavage of a maltooligomer substrate 2-chloro-4-nitrophenyl-β-D-maltoheptoside. Measurement of chromophore containing products after reversed phase HPLC separation was used for α-amylase activity measurement...
June 2017: Acta Biologica Hungarica
https://www.readbyqxmd.com/read/28596971/soluble-urokinase-receptor-and-the-kidney-response-in-diabetes-mellitus
#15
REVIEW
Ranadheer R Dande, Vasil Peev, Mehmet M Altintas, Jochen Reiser
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) worldwide. DN typically manifests by glomerular hyperfiltration and microalbuminuria; then, the disease progresses to impaired glomerular filtration rate, which leads to ESRD. Treatment options for DN include the strict control of blood glucose levels and pressure (e.g., intraglomerular hypertension). However, the search for novel therapeutic strategies is ongoing. These include seeking specific molecules that contribute to the development and progression of DN to potentially interfere with these "molecular targets" as well as with the cellular targets within the kidney such as podocytes, which play a major role in the pathogenesis of DN...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28596919/rho-kinase-rock-as-a-potential-drug-target-for-vitreoretinal-diseases
#16
REVIEW
Muneo Yamaguchi, Shintaro Nakao, Mitsuru Arima, Iori Wada, Yoshihiro Kaizu, Feng Hao, Shigeo Yoshida, Koh-Hei Sonoda
Rho-associated kinase (Rho-kinase/ROCK) was originally identified as an effector protein of the G protein Rho. Its involvement in various diseases, particularly cancer and cardiovascular disease, has been elucidated, and ROCK inhibitors have already been applied clinically for cerebral vasospasm and glaucoma. Vitreoretinal diseases including diabetic retinopathy, age-related macular degeneration, and proliferative vitreoretinoapthy are still a major cause of blindness. While anti-VEGF therapy has recently been widely used for vitreoretinal disorders due to its efficacy, attention has been drawn to new unmet needs...
2017: Journal of Ophthalmology
https://www.readbyqxmd.com/read/28595520/a-case-of-fulminant-type-1-diabetes-following-anti-pd1-immunotherapy-in-a-genetically-susceptible-patient
#17
Manuel Araújo, Dário Ligeiro, Luís Costa, Filipa Marques, Helder Trindade, José Manuel Correia, Candida Fonseca
Programmed cell death-1 protein (PD-1) is an immune checkpoint that has gained popularity in the treatment of several advanced cancers. Inhibiting this checkpoint is known to enhance immune response, but is also known to diminish immune tolerance and to increase autoimmune toxicity. We discuss a case of rapid onset fulminant Type 1 diabetes induced by treatment with anti-programmed cell death-1 monoclonal antibody, nivolumab, in a patient with late-stage non-small-cell lung adenocarcinoma. The patient had no history of previous diabetes but did reveal a high-risk genotype for Type 1 diabetes development (DR3-DQ2; DR4-DQ8)...
June 2017: Immunotherapy
https://www.readbyqxmd.com/read/28594337/-op-1c-08-hemodynamic-parameters-in-hypertensive-diabetic-patients
#18
A Yannoutsos, M Ahouah, C Dreyfuss Tubiana, J Topouchian, C Touboul, M Safar, J Blacher
OBJECTIVE: Despite adequate glycemic and blood pressure (BP) control, diabetic hypertensives remain at increased cardiovascular (CV) risk. Aortic stiffness and pulse pressure (PP) amplification may provide complementary information to correct CV risk. We aim to determine whether these hemodynamic parameters are interrelated or not and to explore the factors related to pressure pulsatility.(Figure is included in full-text article.)DESIGN AND METHOD:: A cross-sectional study was conducted in 351 patients, involving controls, hypertensives without diabetes and diabetic patients with or without hypertension...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/28594069/glucose-targets-for-preventing-diabetic-kidney-disease-and-its-progression
#19
REVIEW
Marinella Ruospo, Valeria M Saglimbene, Suetonia C Palmer, Salvatore De Cosmo, Antonio Pacilli, Olga Lamacchia, Mauro Cignarelli, Paola Fioretto, Mariacristina Vecchio, Jonathan C Craig, Giovanni Fm Strippoli
BACKGROUND: Diabetes is the leading cause of end-stage kidney disease (ESKD) around the world. Blood pressure lowering and glucose control are used to reduce diabetes-associated disability including kidney failure. However there is a lack of an overall evidence summary of the optimal target range for blood glucose control to prevent kidney failure. OBJECTIVES: To evaluate the benefits and harms of intensive (HbA1c < 7% or fasting glucose levels < 120 mg/dL versus standard glycaemic control (HbA1c ≥ 7% or fasting glucose levels ≥ 120 mg/dL for preventing the onset and progression of kidney disease among adults with diabetes...
June 8, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28593583/regulating-autophagy-as-a-therapeutic-target-for-diabetic-nephropathy
#20
REVIEW
Munehiro Kitada, Yoshio Ogura, Itaru Monno, Daisuke Koya
PURPOSE OF REVIEW: Autophagy promotes cellular health in response to various cellular stresses and to changes in nutrient conditions. In this review, we focus on the role of autophagy in the pathogenesis of diabetic nephropathy and discuss the regulation of autophagy as a new therapeutic target for the suppression of diabetic nephropathy. RECENT FINDINGS: Previous studies have indicated that autophagy deficiency or insufficiency in renal cells, including podocytes, mesangial cells, endothelial cells and tubular cells, contributes to the pathogenesis of diabetic nephropathy...
July 2017: Current Diabetes Reports
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