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GLP1 agonist

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https://www.readbyqxmd.com/read/28213092/prediction-of-thyroid-c-cell-carcinogenicity-after-chronic-administration-of-glp1-r-agonists-in-rodents
#1
Willem van den Brink, Annette Emerenciana, Francesco Bellanti, Oscar Della Pasqua, Jan Willem van der Laan
Increased incidence of C-cell carcinogenicity has been observed for glucagon-like-protein-1 receptor (GLP-1r) agonists in rodents. It is suggested that the duration of exposure is an indicator of carcinogenic potential in rodents of the different products on the market. Furthermore, the role of GLP-1-related mechanisms in the induction of C-cell carcinogenicity has gained increased attention by regulatory agencies. This study proposes an integrative pharmacokinetic/pharmacodynamic (PKPD) framework to identify explanatory factors and characterize differences in carcinogenic potential of the GLP-1r agonist products...
February 16, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28202906/bar502-a-dual-fxr-and-gpbar1-agonist-promotes-browning-of-white-adipose-tissue-and-reverses-liver-steatosis-and-fibrosis
#2
Adriana Carino, Sabrina Cipriani, Silvia Marchianò, Michele Biagioli, Chiara Santorelli, Annibale Donini, Angela Zampella, Maria Chiara Monti, Stefano Fiorucci
Non-alcoholic steatohepatitis (NASH) is a highly prevalent chronic liver disease. Here, we have investigated whether BAR502, a non-bile acid, steroidal dual ligand for FXR and GPBAR1, reverses steato-hepatitis in mice fed a high fat diet (HFD) and fructose. After 9 week, mice on HFD gained ≈30% of b.w (P < 0.01 versus naïve) and were insulin resistant. These overweighting and insulin resistant mice were randomized to receive HFD or HFD in combination with BAR502. After 18 weeks, HFD mice developed NASH like features with severe steato-hepatitis and fibrosis, increased hepatic content of triacylglycerol and cholesterol and expression of SREPB1c, FAS, ApoC2, PPARα and γ, α-SMA, α1 collagen and MCP1 mRNAs...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28164753/evaluation-of-the-influence-of-the-conjugation-site-of-the-chelator-agent-hynic-to-glp1-antagonist-radiotracer-for-insulinoma-diagnosis
#3
Bluma Linkowski Faintuch, Daniele Seo, Érica Aparecida De Oliveira, Roselaine Campos Targino, Ana Maria Moro
Radiotracer diagnosis of insulinoma, can be done using somatostatin or glucagon-like peptide 1 (GLP-1). Performance of GLP-1 antagonists tends to be better than of agonists. We investigated the uptake of the antagonist exendin (9-39), radiolabeled with technetium-99m. Two different sites of the biomolecule were selected for chelator attachment. HYNIC-βAla chelator attached to serine (C- terminus) of exendin, was associated with higher tumor uptake than to aspartate (N- terminus). In conclusion the chelator position in the biomolecule influenced receptor uptake...
January 26, 2017: Current Radiopharmaceuticals
https://www.readbyqxmd.com/read/28105738/glucagon-like-peptide-1-agonists-and-risk-of-acute-pancreatitis-in-patients-with-type-2-diabetes
#4
Heidi Storgaard, Frederik Cold, Lise L Gluud, Tina Vilsbøll, Filip K Knop
Glucagon-like peptide-1 receptor agonist (GLP-1RAs) labels warn about acute pancreatitis (AP) and impose doctors to inform patients about symptoms of AP. Here we systematically reviewed the risk of AP in randomized placebo-controlled trials (RCTs) investigating the effect of GLP-1RAs in type 2 diabetes. We performed a systematic review with meta-analysis of long-term (minimum 24 months), placebo-controlled GLP-1RA RCTs in which AP was a predefined adverse event and adjudicated by blinded and independent adjudicating committees...
January 20, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28077257/real-world-effectiveness-and-safety-of-dapagliflozin-therapy-added-to-a-glp1-receptor-agonist-in-patients-with-type-2-diabetes
#5
J J Gorgojo-Martínez, C Serrano-Moreno, A Sanz-Velasco, G Feo-Ortega, F Almodóvar-Ruiz
BACKGROUND AND AIM: To evaluate the effectiveness and safety of a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, dapagliflozin, in patients with type 2 diabetes mellitus (T2DM) and background glucagon-like peptide-1 receptor agonist (GLP1-RA) therapy. METHODS AND RESULTS: This is a 12-month, real-world observational study, which assessed the effectiveness and safety of dapagliflozin in patients with T2DM and background GLP1-RA therapy. The main outcome measures were changes in A1C and weight at 6 and 12 months from baseline...
November 23, 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/27903028/-cardiovascular-morbidity-and-mortality-in-patients-with-kidney-disease
#6
Ivo Quack, Ralf Westenfeld
Patients with kidney disease have a significantly increased cardiovascular morbidity and mortality. Especially diabetics have an increased risk to develop renal insufficiency and cardiovascular events. Two recent studies show that the SGLT2 inhibitor Empagliflozin and the GLP1 agonist Liraglutid are able to lower the cardiovascular risk of type2 diabetics with renal insufficiency. Recent observations suggest that bradycardia and asystole are main triggers for sudden cardiac death in patients with chronic kidney disease...
November 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27872157/exendin-4-increases-oxygen-consumption-and-thermogenic-gene-expression-in-muscle-cells
#7
Jin-Seung Choung, Young-Sun Lee, Hee-Sook Jun
Glucagon-like peptide-1 (GLP1) has many anti-diabetic actions and also increases energy expenditure in vivo As skeletal muscle is a major organ controlling energy metabolism, we investigated whether GLP1 can affect energy metabolism in muscle. We found that treatment of differentiated C2C12 cells with exendin-4 (Ex-4), a GLP1 receptor agonist, reduced oleate:palmitate-induced lipid accumulation and triglyceride content compared with cells without Ex-4 treatment. When we examined the oxygen consumption rate (OCR), not only the basal OCR but also the OCR induced by oleate:palmitate addition was significantly increased in Ex-4-treated differentiated C2C12 cells, and this was inhibited by exendin-9, a GLP1 receptor antagonist...
February 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/27780892/diabetes-negatively-affects-cortical-and-striatal-gabaergic-neurons-an-effect-that-is-partially-counteracted-by-exendin-4
#8
Martin Larsson, Grazyna Lietzau, David Nathanson, Claes-Göran Östenson, Carina Mallard, Maria E Johansson, Thomas Nyström, Cesare Patrone, Vladimer Darsalia
Type 2 diabetic (T2D) patients often develop early cognitive and sensorimotor impairments. The pathophysiological mechanisms behind these problems are largely unknown. Recent studies demonstrate that dysfunctional γ-aminobutyric acid (GABAergic) neurons are involved in age-related cognitive decline. We hypothesized that similar, but earlier dysfunction is taking place under T2D in the neocortex and striatum (two brain areas important for cognition and sensorimotor functions). We also hypothesized that the T2D-induced effects are pharmacologically reversible by anti-diabetic drugs targeting the glucagon-like peptide-1 receptor (GLP-1R)...
December 2016: Bioscience Reports
https://www.readbyqxmd.com/read/27633289/can-glucagon-like-peptide-1-glp1-agonists-or-sodium-glucose-co-transporter-2-sglt2-inhibitors-ameliorate-non-alcoholic-steatohepatitis-in-people-with-or-without-diabetes
#9
Vasilios G Athyros, Niki Katsiki, Asterios Karagiannis
No abstract text is available yet for this article.
September 9, 2016: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/27627094/-glucagon-antagonists-open-a-new-way-in-treatment-of-type-2-diabetes-mellitus
#10
Karel Vondra
UNLABELLED: Excessive hepatic glucose production resulting from dysregulated glucagon secretion associated with inappropriate fasting and postprandial hyperglucagonemia is common feature in type 2 diabetes (DM2T). The effects of some currently widely used anti-diabetic agents, especially concerning metformin, GLP1 agonists and inhibitors of DPP4, comprise partial supression of glucagon secretion and/or action. Complete supression of glucagon action is recently widely investigated in experiments, and also results of phase 1 and 2 of the clinical trials are available...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27593966/inkt-cells-induce-fgf21-for-thermogenesis-and-are-required-for-maximal-weight-loss-in-glp1-therapy
#11
Lydia Lynch, Andrew E Hogan, Danielle Duquette, Chantel Lester, Alexander Banks, Katherine LeClair, David E Cohen, Abhisek Ghosh, Bing Lu, Michelle Corrigan, Darko Stevanovic, Eleftheria Maratos-Flier, Daniel J Drucker, Donal O'Shea, Michael Brenner
Adipose-resident invariant natural killer T (iNKT) cells are key players in metabolic regulation. iNKT cells are innate lipid sensors, and their activation, using their prototypic ligand α-galactosylceramide (αGalCer), induces weight loss and restores glycemic control in obesity. Here, iNKT activation induced fibroblast growth factor 21 (FGF21) production and thermogenic browning of white fat. Complete metabolic analysis revealed that iNKT cell activation induced increased body temperature, V02, VC02, and fatty acid oxidation, without affecting food intake or activity...
September 13, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27577947/gut-microbiota-of-obese-type-2-diabetic-individuals-is-enriched-in-faecalibacterium-prausnitzii-akkermansia-muciniphila-and-peptostreptococcus-anaerobius-after-weight-loss
#12
Marlene Remely, Berit Hippe, Julia Zanner, Eva Aumueller, Helmuth Brath, Alexander G Haslberger
Beside the influence of nutritional habits and reduced physical activity, metabolic syndrome is associated with alterations in the structure of gut microbiota influencing the inflammatory immune responses. Gut microbiota and microbial metabolic activities are known to affect the lipid and glucose metabolism, satiety and chronic low-grade inflammation in the metabolic syndrome. The aim of the study was to identify genera or even species affecting host metabolism in obesity and type 2 diabetes beside the commonly used indicator: Firmicutes/Bacteroidetes ratio...
August 30, 2016: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/27447052/glucagon-like-peptide-1-receptor-a-novel-pharmacological-target-for-treating-human-bronchial-hyperresponsiveness
#13
Paola Rogliani, Luigino Calzetta, Barbara Capuani, Francesco Facciolo, Mario Cazzola, Davide Lauro, Maria Gabriella Matera
Asthma is associated with several comorbidities, such as type 2 diabetes mellitus, which may lead to bronchial hyperresponsiveness (BHR). Because glucagon-like peptide (GLP) 1 regulates glucose homeostasis, we pharmacologically investigated the influence of the GLP1 receptor (GLP1-R) agonist, exendin-4, on BHR induced in human isolated airways. The effect of exendin-4 was assessed in human isolated airways undergoing overnight passive sensitization and high-glucose stimulation, two conditions mimicking ex vivo the BHR typical of patients with asthma and diabetes, respectively...
December 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27373139/novel-antidiabetic-drugs-and-cardiovascular-risk-primum-non-nocere
#14
R C Bonadonna, C Borghi, A Consoli, M Volpe
AIMS: Diabetes treatments aim at preventing undesirable metabolic effects of hyperglycemia and at preventing/reducing tissue damage, including cardiovascular (CV) events. For approval, novel diabetes drugs undergo early systematic investigation to assess CV safety. This review provides an updated analysis of the results of recent studies examining novel diabetes medications and CV outcomes. DATA SYNTHESIS: The new regulatory guidelines enforce adjudication of all CV events when testing novel diabetes drugs...
September 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/27368005/comparative-effectiveness-of-incretin-based-therapies-and-the-risk-of-death-and-cardiovascular-events-in-38-233-metformin-monotherapy-users
#15
COMPARATIVE STUDY
John-Michael Gamble, Jamie M Thomas, Laurie K Twells, William K Midodzi, Sumit R Majumdar
There is limited comparative effectiveness evidence to guide approaches to managing diabetes in individuals failing metformin monotherapy. Our aim was to compare the incidence of all-cause mortality and major adverse cardiovascular events (MACEs) among new metformin monotherapy users initiating a dipeptidyl-peptidase-4 inhibitor (DPP4i), glucagon-like peptide-1 receptor agonist (GLP-1RA), sulfonylurea (SU), thiazolidinedione, or insulin.We conducted a cohort study using the UK-based Clinical Practice Research Datalink...
June 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27340935/glp1-ra-add-on-therapy-in-patients-with-type-2-diabetes-currently-on-a-bolus-containing-insulin-regimen
#16
REVIEW
Marie L Davies, David Q Pham, Scott R Drab
Adding glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to basal insulin regimens has become a guideline-recommended treatment option for uncontrolled type 2 diabetes. However, limited data exist to support the use of GLP-1 RAs with insulin regimens, including bolus insulin in patients with type 2 diabetes. The primary objectives of this review were to identify if the combination of a GLP-1 RA and an insulin regimen containing bolus insulin resulted in improvements in HbA1c , weight loss, reduction in insulin doses, and to evaluate the side effect profile of this combination in terms of nausea and hypoglycemia risk...
August 2016: Pharmacotherapy
https://www.readbyqxmd.com/read/26652966/-clinical-and-economic-benefits-of-the-new-antidiabetic-drugs-in-the-czech-republic
#17
Tomáš Doležal, Klára Kruntorádová
GOAL: Description of efficiency, safety and cost-effectiveness of the therapy with new antidiabetics from the incretins group for the patients whose treatment with DPP4 inhibitors and GLP1 receptor agonists respectively, commenced based on the real data from the routine clinical practice in the Czech Republic. METHODOLOGY: Collection of clinical data before the commencement of treatment and in the following 12 months. The following data was collected for all patients: demographic data, time elapsed from diagnosis, body weight, BMI, HbA1c, systolic and diastolic blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides...
November 2015: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/26652965/-the-prorok-project-results-after-6-months-of-intervention-prospective-observation-project-focusing-on-the-relevance-of-the-difference-between-fasting-blood-glucose-levels-and-postprandial-blood-glucose-for-estimation-of-success-of-type-2-diabetes-therapy
#18
Denisa Janíčková -Žďarská, Pavlína Piťhová, Tomáš Pavlík, Milan Kvapil
INTRODUCTION: The PROROK project (Prospective observation project focusing on the relevance of the difference between fasting and postprandial blood glucose levels for the estimation of success of type 2 diabetes therapy) had a character of non-interventional, prospective, multicentric observation study lasting 6 months, whose goal was to quantify the relevance of the difference between fasting and postprandial blood glucose levels to the success of the treatment with GLP1 receptor agonists, resp...
November 2015: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/26455904/incretin-actions-and-consequences-of-incretin-based-therapies-lessons-from-complementary-animal-models
#19
REVIEW
Simone Renner, Andreas Blutke, Elisabeth Streckel, Rüdiger Wanke, Eckhard Wolf
The two incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP1), were discovered 45 and 30 years ago. Initially, only their insulinotropic effect on pancreatic β cells was known. Over the years, physiological and pharmacological effects of GIP and GLP1 in numerous extrapancreatic tissues were discovered which partially overlap, but may also be specific for GIP or GLP1 in certain target tissues. While the insulinotropic effect of GIP was found to be blunted in patients with type 2 diabetes, the function of GLP1 is preserved and GLP1 receptor agonists and dipeptidyl-peptidase 4 (DPP4) inhibitors, which prolong the half-life of incretins, are widely used in diabetes therapy...
January 2016: Journal of Pathology
https://www.readbyqxmd.com/read/26271795/comparison-review-of-short-acting-and-long-acting-glucagon-like-peptide-1-receptor-agonists
#20
Annachiara Uccellatore, Stefano Genovese, Ilaria Dicembrini, Edoardo Mannucci, Antonio Ceriello
Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) are useful tools for treating type 2 diabetes mellitus. In their recent position statement, the American Diabetes Association and European Association for the Study of Diabetes recommend GLP1-RAs as add-on to metformin when therapeutic goals are not achieved with monotherapy, particularly for patients who wish to avoid weight gain or hypoglycemia. GLP1-RAs differ substantially in their duration of action, frequency of administration and clinical profile...
September 2015: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
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