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Glp 1 agonist

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https://www.readbyqxmd.com/read/28533434/lysophosphatidylinositol-induced-activation-of-the-cation-channel-trpv2-triggers-glucagon-like-peptide-1-secretion-in-enteroendocrine-l-cells
#1
Kazuki Harada, Tetsuya Kitaguchi, Taichi Kamiya, Kyaw Htet Aung, Kazuaki Nakamura, Kunihiro Ohta, Takashi Tsuboi
The lysophosphatidylinositol (LPI) has crucial roles in multiple physiological processes, including insulin exocytosis from pancreatic islets. However, the role of LPI in secretion of glucagon like peptide-1 (GLP-1), a hormone that enhances glucose-induced insulin secretion, is unclear. Here, we used the murine enteroendocrine L cell line GLUTag and primary murine small intestinal cells to elucidate the mechanism of LPI-induced GLP-1 secretion. Exogenous LPI addition increased intracellular Ca2+ concentrations ([Ca2+]i) in GLUTag cells and induced GLP-1 secretion from both GLUTag and acutely prepared primary intestinal cells...
May 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28533296/glp-1r-as-a-target-for-the-treatment-of-diabetic-retinopathy-friend-or-foe
#2
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/28528456/pharmacologic-treatment-of-dyslipidemia-in-diabetes-a-case-for-therapies-in-addition-to-statins
#3
REVIEW
Abeer Anabtawi, Patrick M Moriarty, John M Miles
PURPOSE OF REVIEW: The purpose of the study is to review the use of statins and the role of both non-statin lipid-lowering agents and diabetes-specific medications in the treatment of diabetic dyslipidemia. RECENT FINDINGS: Statins have a primary role in the treatment of dyslipidemia in people with type 2 diabetes, defined as triglyceride levels >200 mg/dl and HDL cholesterol levels <40 mg/dL. A number of clinical trials suggest that treatment with a fibrate may reduce cardiovascular events...
July 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28526416/treatment-strategy-for-type-2-diabetes-with-obesity-focus-on-glucagon-like-peptide-1-receptor-agonists
#4
REVIEW
Qiuhe Ji
PURPOSE: The progressive nature of type 2 diabetes mellitus (T2DM) calls for step-wise intensification of therapy for maintaining normal glycemic levels and lowering cardiovascular (CV) risk. Because obesity is a prominent risk factor and comorbidity of T2DM, it further elevates the CV risk in T2DM. Therefore, it is vital to manage weight, obesity, and glycemic parameters for effective T2DM management. Few oral antidiabetic drugs (sulfonylureas and thiazolidinediones) and insulin are not suitable for obese patients with T2DM because these drugs cause weight gain...
May 16, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28523587/erratum-to-glucagon-like-peptide-1-receptor-agonists-glp-1ras-in-the-brain-adipocyte-axis
#5
Bruno Geloneze, José Carlos de Lima-Júnior, Lício A Velloso
No abstract text is available yet for this article.
May 18, 2017: Drugs
https://www.readbyqxmd.com/read/28523577/ffa3-activation-stimulates-duodenal-bicarbonate-secretion-and-prevents-nsaid-induced-enteropathy-via-the-glp-2-pathway-in-rats
#6
Hyder Said, Yasutada Akiba, Kazuyuki Narimatsu, Koji Maruta, Ayaka Kuri, Ken-Ichi Iwamoto, Atsukazu Kuwahara, Jonathan D Kaunitz
BACKGROUND: Therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with enteropathy in humans and experimental animals, a cause of considerable morbidity. Unlike foregut NSAID-associated mucosal lesions, most treatments for this condition are of little efficacy. We propose that the endogenously released intestinotrophic hormone glucagon-like peptide-2 (GLP-2) prevents the development of NSAID-induced enteropathy. Since the short-chain fatty acid receptor FFA3 is expressed on enteroendocrine L cells and on enteric nerves in the gastrointestinal tract, we further hypothesized that activation of FFA3 on L cells protects the mucosa from injury via GLP-2 release with enhanced duodenal HCO3(-) secretion...
May 18, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28523483/modeling-the-long-term-cost-effectiveness-of-ideglira-in-patients-with-type-2-diabetes-who-are-failing-to-meet-glycemic-targets-on-basal-insulin-alone-in-the-netherlands
#7
Barnaby Hunt, Divina Glah, Maarten van der Vliet
INTRODUCTION: Insulin degludec/liraglutide (IDegLira) is the first basal insulin and glucagon-like peptide-1 receptor agonist (GLP-1 RA) in a single pen injection device, and a once-daily treatment option for patients with type 2 diabetes mellitus (T2DM) who are uncontrolled on basal insulin and require treatment intensification. The objective of this analysis was to evaluate the long-term cost-effectiveness of IDegLira versus basal-bolus therapy (insulin glargine U100 + 3× daily insulin aspart) for patients with T2DM uncontrolled on basal insulin [HbA1c >53 mmol/mol (>7%)] in the Netherlands...
May 18, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28522196/impact-of-glucose-lowering-therapies-on-risk-of-stroke-in-type-2-diabetes
#8
REVIEW
F Bonnet, A J Scheen
Patients with type 2 diabetes (T2D) have an increased risk of stroke compared with people without diabetes. However, the effects of glucose-lowering drugs on risk of ischaemic stroke in T2D have been less extensively investigated than in coronary heart disease. Some evidence, including the UKPDS, has suggested a reduced risk of stroke with metformin, although the number of studies is limited. Inhibition of the KATP channels increases ischaemic brain lesions in animals. This is in agreement with a recent meta-analysis showing an increased risk of stroke with sulphonylureas vs...
May 15, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28515711/the-impact-of-glucagon-like-peptide-1-on-bone-metabolism-and-its-possible-mechanisms
#9
REVIEW
Chenhe Zhao, Jing Liang, Yinqiu Yang, Mingxiang Yu, Xinhua Qu
The impact of antidiabetic drugs on bone metabolism is drawing increasing attention due to the discovery of a correlation between type 2 diabetes mellitus (T2DM) and osteoporosis. Glucagon-like peptide-1 (GLP-1) receptor agonists are a novel and promising class of drugs for T2DM, which may also have clinical applications in bone tissue disorders. This review examines the impact of GLP-1 on bone metabolism, including enhancement of bone mineral density and improvement of bone quality. However, the precise effect of GLP-1 on fracture risk has not been unambiguously defined...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28514449/human-glp-1-receptor-transmembrane-domain-structure-in-complex-with-allosteric-modulators
#10
Gaojie Song, Dehua Yang, Yuxia Wang, Chris de Graaf, Qingtong Zhou, Shanshan Jiang, Kaiwen Liu, Xiaoqing Cai, Antao Dai, Guangyao Lin, Dongsheng Liu, Fan Wu, Yiran Wu, Suwen Zhao, Li Ye, Gye Won Han, Jesper Lau, Beili Wu, Michael A Hanson, Zhi-Jie Liu, Ming-Wei Wang, Raymond C Stevens
The glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR) are members of the secretin-like class B family of G-protein-coupled receptors (GPCRs) and have opposing physiological roles in insulin release and glucose homeostasis. The treatment of type 2 diabetes requires positive modulation of GLP-1R to inhibit glucagon secretion and stimulate insulin secretion in a glucose-dependent manner. Here we report crystal structures of the human GLP-1R transmembrane domain in complex with two different negative allosteric modulators, PF-06372222 and NNC0640, at 2...
May 17, 2017: Nature
https://www.readbyqxmd.com/read/28507313/chronic-intrahypothalamic-rather-than-subcutaneous-liraglutide-treatment-reduces-body-weight-gain-and-stimulates-the-melanocortin-receptor-system
#11
K Kaineder, T Birngruber, G Rauter, B Obermüller, J Eichler, J Münzker, W Al-Zoughbi, S I Mautner, S S Torekov, B Hartmann, P Kotzbeck, T R Pieber
BACKGROUND: The GLP-1 receptor agonist liraglutide is marketed for obesity treatment where it induces body weight reduction possibly via the hypothalamus, which regulates energy homeostasis. In animal studies, acute liraglutide treatment triggers satiety, weight loss and activates thermogenesis in adipose tissue. However, the precise mechanisms how liraglutide affects in particular chronic weight loss are still under investigation. OBJECTIVES: We aimed to evaluate whether chronic hypothalamic or chronic subcutaneous administration of liraglutide induces sustained weight loss through altered adipose tissue function and to what extent hypothalamic neuronal appetite regulators are involved in the liraglutide-induced weight loss in healthy lean rats on a normal diet...
April 25, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28501906/medication-use-for-the-treatment-of-diabetes-in-obese-individuals
#12
REVIEW
John P H Wilding
Obesity is a major cause of type 2 diabetes and may complicate type 1 diabetes. Weight loss for obese individuals with diabetes has many health benefits, often leads to improvement in glucose control and sometimes, in type 2 diabetes, near normalisation of abnormal glucose metabolism. Weight loss is difficult to maintain and attempts to lose weight may be undermined by some diabetes treatments such as sulfonylureas, thiazolidinediones and insulin. Whilst lifestyle support should be the primary approach to aid individuals who wish to lose weight, pharmacological approaches can also be considered...
May 14, 2017: Diabetologia
https://www.readbyqxmd.com/read/28501352/effects-of-glucagon-like-peptide-1-receptor-agonists-on-mortality-and-cardiovascular-events-a-comprehensive-meta-analysis-of-randomized-controlled-trials
#13
Matteo Monami, Stefania Zannoni, Laura Pala, Antonio Silverii, Francesco Andreozzi, Giorgio Sesti, Edoardo Mannucci
INTRODUCTION: The publication of the results of LEADER and SUSTAIN-6 trials suggested a possible beneficial effect of the class of GLP-1 receptor agonists on cardiovascular morbidity and mortality. The aim of the present meta-analysis is to collect and synthetize all available evidence on the effect of GLP-1 receptor agonists on cardiovascular events and mortality. METHODS: A Medline search for GLP-1 receptor agonists (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, or semaglutide) was performed, collecting all randomized clinical trials with a duration >11weeks, enrolling patients with type 2 diabetes, and comparing a GLP-1 receptor agonist with placebo or any other non-GLP-1 receptor agonist drug...
May 5, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28479155/treatment-with-glp1-receptor-agonists-reduce-serum-crp-concentrations-in-patients-with-type-2-diabetes-mellitus-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#14
REVIEW
Mohsen Mazidi, Ehsan Karimi, Peyman Rezaie, Gordon A Ferns
AIM: To undertake a systematic review and meta-analysis of randomized controlled trials of the effect of glucagon-like peptide-1 receptor agonist (GLP-1 RAs) therapy on serum C-reactive protein (CRP) concentrations. METHOD: PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases were searched for the period up until March 16, 2016. Prospective studies evaluating the impact of GLP-1 RAs on serum CRP were identified. A random effects model (using the DerSimonian-Laird method) and generic inverse variance methods were used for quantitative data synthesis...
May 30, 2016: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28474401/a-review-of-glucagon-like-peptide-1-receptor-agonists-and-their-effects-on-lowering-postprandial-plasma-glucose-and-cardiovascular-outcomes-in-the-treatment-of-type-2-diabetes-mellitus
#15
REVIEW
D R Owens, L Monnier, M Hanefeld
Type 2 diabetes mellitus (T2DM) is an independent risk factor for cardiovascular (CV) comorbidities, with CV disease being the most common cause of death in adults with T2DM. Although glucocentric therapies may improve glycaemic control (as determined by glycated haemoglobin levels), evidence suggests that this approach alone has limited beneficial effects on CV outcomes relative to improvements in lipid and blood pressure control. This may be explained in part by the fact that current antidiabetic treatment regimens primarily address overall glycaemia and/or fasting plasma glucose, but not the postprandial plasma glucose (PPG) excursions that have a fundamental causative role in increasing CV risk...
May 4, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28473471/are-targeted-therapies-for-diabetic-cardiomyopathy-on-the-horizon
#16
REVIEW
Mitchel Tate, David J Grieve, Rebecca H Ritchie
Diabetes increases the risk of heart failure approximately 2.5-fold, independent of coronary artery disease and other comorbidities. This process, termed diabetic cardiomyopathy, is characterized by initial impairment of left ventricular (LV) relaxation followed by LV contractile dysfunction. Post-mortem examination reveals that human diastolic dysfunction is closely associated with LV damage, including cardiomyocyte hypertrophy, apoptosis and fibrosis, with impaired coronary microvascular perfusion. The pathophysiological mechanisms underpinning the characteristic features of diabetic cardiomyopathy remain poorly understood, although multiple factors including altered lipid metabolism, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum (ER) stress, inflammation, as well as epigenetic changes, are implicated...
May 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28472488/geographical-variation-in-anti-diabetic-prescribing-in-ireland-in-2013-and-2014-a-cross-sectional-analysis
#17
Mark E Murphy, Kathleen Bennett, Tom Fahey, Susan M Smith
Background.: Several new medications for type 2 diabetes (T2DM) have been introduced, including dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 receptor (GLP-1) agonists. Variation in the prescribing of these agents has implications for quality, safety and costs. We aimed to investigate geographical variation in the prescribing of anti-diabetic medications in Ireland. Methods.: Cross-sectional analyses were undertaken on the two main national pharmacy claims databases in Ireland in 2013 and 2014...
May 2, 2017: Family Practice
https://www.readbyqxmd.com/read/28470000/input-estimation-for-extended-release-formulations-exemplified-with-exenatide
#18
Magnus Trägårdh, Michael J Chappell, Johan E Palm, Neil D Evans, David L I Janzén, Peter Gennemark
Estimating the in vivo absorption profile of a drug is essential when developing extended-release medications. Such estimates can be obtained by measuring plasma concentrations over time and inferring the absorption from a model of the drug's pharmacokinetics. Of particular interest is to predict the bioavailability-the fraction of the drug that is absorbed and enters the systemic circulation. This paper presents a framework for addressing this class of estimation problems and gives advice on the choice of method...
2017: Frontiers in Bioengineering and Biotechnology
https://www.readbyqxmd.com/read/28463898/glucose-kinetics-an-update-and-novel-insights-into-its-regulation-by-glucagon-and-glp-1
#19
Amalia Gastaldelli, Melania Gaggini, Ralph DeFronzo
PURPOSE OF REVIEW: Glucagon and GLP-1 share the same origin (i.e., proglucagon); primarily GLP-1 is generated from intestinal L-cells and glucagon from pancreatic α-cell, but intestinal glucagon and pancreatic GLP-1 secretion is likely. Glucose kinetics are tightly regulated by pancreatic hormones insulin and glucagon, but other hormones, including glucagon-like peptide-1 (GLP-1), also play an important role. The purpose of this review is to describe the recent findings on the mechanisms by which these two hormones regulate glucose kinetics...
April 29, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28461341/pglp-1-a-novel-long-acting-dual-function-glp-1-analog-ameliorates-streptozotocin-induced-hyperglycemia-and-inhibits-body-weight-loss
#20
Huashan Gao, Qian Zhao, Ziwei Song, Zhaocong Yang, You Wu, Shanshan Tang, Murad Alahdal, Yanfeng Zhang, Liang Jin
It is well known that glucagon-like peptide 1 (GLP-1) has antidiabetic action. It has 2 distinct functions, an insulinotropic effect dependent on GLP-1 receptor (GLP-1R) and an insulinomimetic effect independent of GLP-1R. However, use of GLP-1 in vivo is limited by its short half-life. Therefore, our lab designed PGLP-1, a novel 2-function candidate peptide as a potential substitute. Using a streptozotocin-induced hyperglycemic mouse model, we demonstrated in vitro and in vivo that PGLP-1 had insulinotropic actions dependent on GLP-1R and insulinomimetic functions independent of GLP-1R...
May 1, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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