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Glp 1 agonist

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https://www.readbyqxmd.com/read/28734203/exenatide-mitigated-diet-induced-vascular-aging-and-atherosclerotic-plaque-growth-in-apoe-deficient-mice-under-chronic-stress
#1
Guang Yang, Yanna Lei, Aiko Inoue, Limei Piao, Lina Hu, Haiying Jiang, Takeshi Sasaki, Hongxian Wu, Wenhu Xu, Chenglin Yu, Guangxian Zhao, Shinyu Ogasawara, Kenji Okumura, Masafumi Kuzuya, Xian-Wu Cheng
BACKGROUND AND AIMS: Exposure to psychosocial stress is a risk factor for cardiovascular disorders. Because the glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonist prevents cardiovascular injury, we investigated the beneficial effects and mechanism of the GLP-1 analogue exenatide on stress-related vascular senescence and atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice fed a high-fat (HF) diet. METHODS: ApoE(-/-) mice fed the HF diet were assigned to non-stressed and immobilized-stress groups for 12 weeks...
July 13, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28733905/glp-1-glucagon-receptor-co-agonism-for-treatment-of-obesity
#2
REVIEW
Miguel A Sánchez-Garrido, Sara J Brandt, Christoffer Clemmensen, Timo D Müller, Richard D DiMarchi, Matthias H Tschöp
Over a relatively short period, obesity and type 2 diabetes have come to represent a large medical and economic burden to global societies. The epidemic rise in the prevalence of obesity has metabolic consequences and is paralleled by an increased occurrence of other diseases, such as diabetes, cancer and cardiovascular complications. Together, obesity and type 2 diabetes constitute one of the more preventable causes of premature death and the identification of novel, safe and effective anti-obesity drugs is of utmost importance...
July 21, 2017: Diabetologia
https://www.readbyqxmd.com/read/28733378/is-it-time-to-change-the-type-2-diabetes-treatment-paradigm-no-metformin-should-remain-the-foundation-therapy-for-type-2-diabetes
#3
Silvio E Inzucchi
Most treatment guidelines, including those from the American Diabetes Association/European Association for the Study of Diabetes and the International Diabetes Federation, suggest metformin be used as the first-line therapy after diet and exercise. This recommendation is based on the considerable body of evidence that has accumulated over the last 30 years, but it is also supported on clinical grounds based on metformin's affordability and tolerability. As such, metformin is the most commonly used oral antihyperglycemic agent in the U...
August 2017: Diabetes Care
https://www.readbyqxmd.com/read/28733377/is-it-time-to-change-the-type-2-diabetes-treatment-paradigm-yes-glp-1-ras-should-replace-metformin-in-the-type-2-diabetes-algorithm
#4
Muhammad Abdul-Ghani, Ralph A DeFronzo
Most treatment guidelines, including those from the American Diabetes Association/European Association for the Study of Diabetes and the International Diabetes Federation, suggest metformin be used as the first-line therapy after diet and exercise. This recommendation is based on the considerable body of evidence that has accumulated over the last 30 years, but it is also supported on clinical grounds based on metformin's affordability and tolerability. As such, metformin is the most commonly used oral antihyperglycemic agent in the U...
August 2017: Diabetes Care
https://www.readbyqxmd.com/read/28730750/improving-type-2-diabetes-mellitus-glycaemic-outcomes-is-possible-without-spending-more-on-medication-lessons-from-the-uk-national-diabetes-audit
#5
Adrian H Heald, Mark Livingston, Nagaraj Malipatil, Michal Becher, Joyce Craig, Mike Stedman, Anthony A Fryer
OBJECTIVES: There is continuing discussion globally about how to optimise outcomes for type 2 diabetes (T2DM) patients. In the UK, national (NICE) guidance was updated in 2016 (NG28). We aimed to determine the factors at a GP practice level that relate to glycaemic control outcome. METHODS: Data was accessed from 4,050 GP practices (GPP) (50% of total) covering 1.6 million T2DM patients in the UK National Diabetes Audit 2013-14 and 2014-15. This reported T2DM population characteristics, services and outcomes, including % total glycaemic control (TGC) (at 67...
July 20, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28724607/renal-hemodynamic-effects-of-glucagon-like-peptide-1-agonist-are-mediated-by-nitric-oxide-but-not-prostaglandin
#6
Scott Culver Thomson, Ali Kashkouli, Zhi Zhao Liu, Prabhleen Singh
The incretin hormone, glucagon like peptide-1 (GLP-1), is known for responding to dietary fat and carbohydrate. It elicits effects on pancreas, gut, and brain to stabilize blood glucose levels. We have previously reported that the GLP-1 agonist, exenatide, vasodilates the kidney and suppresses proximal reabsorption. The present study was undertaken to determine whether the renal effects of exenatide are mediated by nitric oxide (NO) and/or prostaglandins. Inulin clearance (GFR) and urine flow rate (UV) were measured in anesthetized rats before and during exenatide infusion (1 nmol/h iv)...
July 19, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28724168/efficacy-and-safety-of-glp-1-receptor-agonists-across-the-spectrum-of-type-2-diabetes-mellitus
#7
Lawrence A Leiter, Michael A Nauck
For patients with type 2 diabetes mellitus, glucagon-like peptide-1 receptor agonists (GLP-1RAs) generally exert robust glucose-lowering effects that are at least as effective as insulin. As monotherapies, changes from baseline in HbA1c with GLP-1RAs ranged from -1.9 to -0.7% in phase 3 trials. In addition, GLP-1RAs confer a low risk of hypoglycaemia and have a body-weight advantage (changes from baseline ranging from -4.0 to -0.4 kg). There is also evidence of significant reductions in risk for cardiovascular events with some of these agents, with a number of other trials underway...
July 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28722834/effects-of-gip-glp-1-and-glp-1ras-on-bone-cell-metabolism
#8
Morten S S Hansen, Michaela Terencova, Jacob Frølich, Moustapha Kassem, Morten Frost
The relationship between gut and skeleton is increasingly recognised as part of the integrated physiology of the whole organism. The incretin hormones gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted from the intestine in response to nutrient intake and exhibit several physiological functions including regulation of islet hormone secretion and glucose levels. A number of GLP-1 receptor agonists (GLP-1RAs) are currently used in treatment of type 2 diabetes and obesity. However, GIP and GLP-1 cognate receptors are widely expressed suggesting that incretin hormones mediate effects beyond control of glucose homeostasis, and reports on associations between incretin hormones and bone metabolism have emerged...
July 19, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28721686/rationale-for-initiation-and-titration-of-the-basal-insulin-glp-1ra-fixed-ratio-combination-products-ideglira-and-iglarlixi-for-the-management-of-type-2-diabetes
#9
REVIEW
Virginia Valentine, Jennifer Goldman, Jay H Shubrook
Type 2 diabetes (T2D) is a progressive disease affecting glucose regulation and a major cause of morbidity and mortality globally. Many patients are not escalated up the treatment ladder appropriately despite failing to achieve glycemic control, with barriers such as fear of hypoglycemia, weight gain, and treatment burden recognized as factors. Exogenous basal insulin is titrated to address control of fasting plasma glucose and may preserve residual β-cell function, thus promoting a greater endogenous prandial insulin response...
July 18, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28721339/the-role-of-glucagon-like-peptide-1-receptor-agonists-in-the-treatment-of-type-2-diabetes
#10
Erin St Onge, Shannon Miller, Elizabeth Clements, Lindsay Celauro, Ke'la Barnes
The role of GLP-1 agonists in the treatment of type 2 diabetes have been shown to be viable options for add-on therapy in diabetic patients, as well as potential monotherapy options. With six available GLP-1 agents, and new combination products in the pipeline, they are a promising drug class for type 2 diabetic patients, especially due to their extended dosing interval and potential weight loss benefits.
June 2017: Journal of Translational Internal Medicine
https://www.readbyqxmd.com/read/28717164/glucagon-like-peptide-1-reduces-pancreatic-%C3%AE-cell-mass-through-hypothalamic-neural-pathways-in-high-fat-diet-induced-obese-rats
#11
Hisae Ando, Koro Gotoh, Kansuke Fujiwara, Manabu Anai, Seiichi Chiba, Takayuki Masaki, Tetsuya Kakuma, Hirotaka Shibata
We examined whether glucagon-like peptide-1 (GLP-1) affects β-cell mass and proliferation through neural pathways, from hepatic afferent nerves to pancreatic efferent nerves via the central nervous system, in high-fat diet (HFD)-induced obese rats. The effects of chronic administration of GLP-1 (7-36) and liraglutide, a GLP-1 receptor agonist, on pancreatic morphological alterations, c-fos expression and brain-derived neurotrophic factor (BDNF) content in the hypothalamus, and glucose metabolism were investigated in HFD-induced obese rats that underwent hepatic afferent vagotomy (VgX) and/or pancreatic efferent sympathectomy (SpX)...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28711285/anti-il-21-monoclonal-antibody-combined-with-liraglutide-effectively-reverses-established-hyperglycemia-in-mouse-models-of-type-1-diabetes
#12
Anna K Rydén, Nikole R Perdue, Philippe P Pagni, Claire B Gibson, Sowbarnika S Ratliff, Rikke K Kirk, Travis J Friesen, Claus Haase, Ken Coppieters, Matthias G von Herrath, Tamar E Boursalian
Immunotherapy for type 1 diabetes (T1D) has previously focused on suppressing the autoimmune response against pancreatic beta cells to preserve endogenous insulin production and regulate glucose levels. With increased attention toward combination therapy strategies, studies indicate the multifunctional cytokine interleukin-21 (IL-21) may be a suitable target as an immuno-modulatory arm, while glucagon-like peptide-1 receptor (GLP-1R) agonists may be appropriate as a beta cell protective arm in combination therapy for T1D...
July 12, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28710307/is-it-safe-to-acutely-discontinue-insulin-therapy-in-patients-with-chronic-hyperglycaemia-starting-glp-1r-agonists
#13
Julie Omolola Okiro, Catherine Mc Hugh, Abuelmagd Abdalla
We report two patients with chronic hyperglycaemia secondary to type 2 diabetes who developed severe vomiting on d. The first patient was diagnosed with a mixed picture of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS) and the second, with DKA. They were on insulin therapy which was discontinued on commencing d because of inefficacy and weight gain. The HHS patient developed dehydration secondary to vomiting and had lactic acidosis but no other precipitant could be found in either case...
July 14, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28708480/optimizing-diabetes-treatment-in-the-presence-of-obesity
#14
REVIEW
Mary Angelynne Esquivel, M Cecilia Lansang
Evidence of a neurophysiologic mechanism that involves hormones from adipocytes, pancreatic islet cells, and the gastrointestinal tract implicated in both obesity and diabetes has led to a search for drugs that not only either target obesity and diabetes or reduce hemoglobin A1c, but also have weight loss as a potential side effect. The authors review medications approved for the treatment of type 2 diabetes mellitus (including pramlintide, also approved for type 1 diabetes) that also have weight loss as a side effect...
July 2017: Cleveland Clinic Journal of Medicine
https://www.readbyqxmd.com/read/28702330/neonatal-glp1r-activation-limits-adult-adiposity-by-durably-altering-hypothalamic-architecture
#15
Andrea V Rozo, Daniella A Babu, PoMan A Suen, David N Groff, Randy J Seeley, Rebecca A Simmons, Patrick Seale, Rexford S Ahima, Doris A Stoffers
OBJECTIVE: Adult obesity risk is influenced by alterations to fetal and neonatal environments. Modifying neonatal gut or neurohormone signaling pathways can have negative metabolic consequences in adulthood. Here we characterize the effect of neonatal activation of glucagon like peptide-1 (GLP-1) receptor (GLP1R) signaling on adult adiposity and metabolism. METHODS: Wild type C57BL/6 mice were injected with 1 nmol/kg Exendin-4 (Ex-4), a GLP1R agonist, for 6 consecutive days after birth...
July 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28700581/corrigendum-crystal-structure-of-the-glp-1-receptor-bound-to-a-peptide-agonist
#16
Ali Jazayeri, Mathieu Rappas, Alastair J H Brown, James Kean, James C Errey, Nathan J Robertson, Cédric Fiez-Vandal, Stephen P Andrews, Miles Congreve, Andrea Bortolato, Jonathan S Mason, Asma H Baig, Iryna Teobald, Andrew S Doré, Malcolm Weir, Robert M Cooke, Fiona H Marshall
This corrects the article DOI: 10.1038/nature22800.
July 12, 2017: Nature
https://www.readbyqxmd.com/read/28698254/mechanism-based-pharmacokinetic-pharmacodynamic-modeling-of-the-glucagon-like-peptide-1-receptor-agonist-exenatide-to-characterize-its-anti-obesity-effects-in-diet-induced-obese-mice
#17
Shinji Iwasaki, Teruki Hamada, Ikumi Chisaki, Tomohiro Andou, Noriyasu Sano, Atsutoshi Furuta, Nobuyuki Amano
Glucagon-like peptide-1 (GLP-1) analogs lower body weight in humans in addition to their potent anti-diabetic effects. Hence, agonistic targeting of the GLP-1 receptor could be a valid approach to target obesity. However, quantitative analyses of the pharmacokinetic/pharmacodynamic (PK/PD) relationship between GLP-1 analogs and their anti-obesity effect have not been reported in either animals or humans. Therefore, the present study was performed to establish a mechanism-based PK/PD model of GLP-1 receptor agonists using the GLP-1 analog, exenatide, for the development of promising new anti-obesity drugs...
July 11, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28695626/mucosal-glucagon-like-peptide-1-glp-1-responses-are-mediated-by-calcitonin-gene-related-peptide-cgrp-in-the-mouse-colon-and-both-peptide-responses-are-area-specific
#18
I R Tough, R Moodaley, H M Cox
BACKGROUND: Glucagon-like peptide (GLP)-1 is an incretin hormone and its mimetics are proven antidiabetic and antiobesity drugs. GLP-1 exerts antimotility and mucosal proliferative activities but its epithelial ion transport effects are uncharacterized and these may contribute to the gastrointestinal (GI) disturbance, i.e., diarrhea experienced with some GLP-1 mimetics. Our aim was to establish GLP-1 agonist mechanisms and identify potential mucosal mediator(s) in the colonic tissue from C57BL/6J mice...
July 11, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28693828/inhibition-of-plaque-progression-and-promotion-of-plaque-stability-by-glucagon-like-peptide-1-receptor-agonist-serial-in%C3%A2-vivo-findings-from-imap-ivus-in-watanabe-heritable-hyperlipidemic-rabbits
#19
Mitsumasa Sudo, Yuxin Li, Takafumi Hiro, Tadateru Takayama, Masako Mitsumata, Masashi Shiomi, Masahiko Sugitani, Taro Matsumoto, Hiroyuki Hao, Atsushi Hirayama
BACKGROUND AND AIMS: Glucagon-like peptide-1 (GLP-1) is thought to inhibit development of aortic atherosclerosis and plaque formation. However, whether GLP-1 stabilizes fully developed atherosclerotic plaque or alters the complicated plaque composition remains unclarified. METHODS: Ten Watanabe heritable hyperlipidemic (WHHL) rabbits were divided into GLP-1 receptor agonist treatment group and control group. After confirmation of atherosclerotic plaques in brachiocephalic arteries by iMap intravascular ultrasound (iMAP-IVUS), GLP-1 receptor agonist lixisenatide was administered to WHHL rabbits at 30 nmoL/kg/day for 12 weeks by osmotic pump...
June 23, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28685936/adapting-the-glaser-reaction-for-bioconjugation-robust-access-to-structurally-simple-rigid-linkers
#20
Anthony Paul Silvestri, Philip A Cistrone, Philip E Dawson
The copper-mediated coupling between alkynes to generate a structurally efficient, linear 1,3-diyne linkage has been known for over a century. However, the mechanistic requirement for simultaneous Cu(I) and an oxidant has limited its practical utility, especially for complex functional molecules in aqueous solution. We find that addition of a specific bpy-diol ligand protects unprotected peptides from Cu(II) mediated oxidative damage through formation of an insoluble Cu(II) gel which solves the critical challenge of applying the Glaser coupling to substrates that are degraded by Cu(II)...
July 6, 2017: Angewandte Chemie
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