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https://www.readbyqxmd.com/read/28607430/liraglutide-improves-liver-microvascular-dysfunction-in-cirrhosis-evidence-from-translational-studies
#1
Fernanda Cristina de Mesquita, Sergi Guixé-Muntet, Anabel Fernández-Iglesias, Raquel Maeso-Díaz, Sergi Vila, Diana Hide, Martí Ortega-Ribera, José Luís Rosa, Juan Carlos García-Pagán, Jaime Bosch, Jarbas Rodrigues de Oliveira, Jordi Gracia-Sancho
Hepatic stellate cells (HSC) play a key role in the development of chronic liver disease (CLD). Liraglutide, well-established in type 2 diabetes, showed anti-inflammatory and anti-oxidant properties. We evaluated the effects of liraglutide on HSC phenotype and hepatic microvascular function using diverse pre-clinical models of CLD. Human and rat HSC were in vitro treated with liraglutide, or vehicle, and their phenotype, viability and proliferation were evaluated. In addition, liraglutide or vehicle was administered to rats with CLD...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28573765/design-and-baseline-characteristics-of-participants-in-the-researching-cardiovascular-events-with-a-weekly-incretin-in-diabetes-rewind-trial-of-dulaglutide-s-cardiovascular-effects
#2
Hertzel C Gerstein, Helen M Colhoun, Gilles R Dagenais, Rafael Diaz, Mark Lakshmanan, Prem Pais, Jeffrey Probstfield, Matthew C Riddle, Lars Rydén, Denis Xavier, Charles Messan Atisso, Alvaro Avezum, Jan Basile, Namsik Chung, Ignacio Conget, William C Cushman, Edward Franek, Nicolae Hancu, Markolf Hanefeld, Shaun Holt, Petr Jansky, Matyas Keltai, Fernando Lanas, Lawrence A Leiter, Patricio Lopez-Jaramillo, Ernesto German Cardona Munoz, Valdis Pirags, Nana Pogosova, Peter J Raubenheimer, Jonathan Shaw, Wayne H-H Sheu, Theodora Temelkova-Kurktschiev
BACKGROUND: Dulaglutide, a synthetic once-weekly, injectable human glucagon-like peptide 1 (GLP1) analogue lowers blood glucose, body weight, appetite, and blood pressure. Its effect on cardiovascular outcomes is unknown. METHODS: People with type 2 diabetes, aged 50 or older, a HbA1c ≤9.5%, and either a previous cardiovascular (CV) event, evidence of CV disease or ≥ 2 CV risk factors were randomly allocated to a weekly subcutaneous injection of either dulaglutide (1...
June 1, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28556815/the-antidiabetic-mechanisms-of-polyphenols-related-to-increased-glucagon-like-peptide-1-glp1-and-insulin-signaling
#3
REVIEW
J Abraham Domínguez Avila, Joaquín Rodrigo García, Gustavo A González Aguilar, Laura A de la Rosa
Type-2 diabetes mellitus (T2DM) is an endocrine disease related to impaired/absent insulin signaling. Dietary habits can either promote or mitigate the onset and severity of T2DM. Diets rich in fruits and vegetables have been correlated with a decreased incidence of T2DM, apparently due to their high polyphenol content. Polyphenols are compounds of plant origin with several documented bioactivities related to health promotion. The present review describes the antidiabetic effects of polyphenols, specifically related to the secretion and effects of insulin and glucagon-like peptide 1 (GLP1), an enteric hormone that stimulates postprandial insulin secretion...
May 30, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28539721/phytochemical-and-biological-evaluations-of-arum-hygrophilum-boiss-araceae
#4
Fatma U Afifi, Violet Kasabri, Simona Litescu, Ismail F Abaza, Khalid Tawaha
BACKGROUND: Arum hygrophilum is a traditional medicinal plant indigenous to Jordan. The present study explores its phytochemistry, antioxidative, antidiabesity, and antiproliferative potentialities. MATERIALS AND METHODS: Column chromatography and HPLC-MS analysis were used for its phytochemical evaluation. Using leaf crude water and ethanol extracts, the antioxidative capacities, their modulation of pancreatic β-cell proliferation, and insulin secretion as well as glucose diffusion and enzymatic bioassays were evaluated...
April 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28502212/-trends-in-antidiabetic-treatment-prescribed-for-patients-with-type-2-diabetes-in-hungary-between-2001-and-2014-results-from-the-database-analysis-of-the-national-health-insurance-fund
#5
György Jermendy, Zoltán Kiss, György Rokszin, Zsolt Abonyi-Tóth, István Wittmann, Péter Kempler
In the last couple of years, significant developments in antidiabetic treatment have influenced the pharmacological treatment of type 2 diabetes mellitus (T2DM). The aim of this study was to analyze the changes in prescribing patterns of glucose-lowering drugs for T2DM patients in Hungary between 2001 and 2014. The number of patients with newly diagnosed T2DM decreased from 75,700 (2001) to 33,700 (2014), while prevalent T2DM cases continuously increased and plateaued in 2014 with a number of registered patients of 727,000...
May 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28493611/fucoidan-ameliorates-pancreatic-%C3%AE-cell-death-and-impaired-insulin-synthesis-in-streptozotocin-treated-%C3%AE-cells-and-mice-via-a-sirt-1-dependent-manner
#6
Wen-Chun Yu, Yen-Lin Chen, Pai-An Hwang, Tso-Hsiao Chen, Tz-Chong Chou
SCOPE: Several beneficial biological functions of fucoidan (FO) isolated from brown algae have been demonstrated. The purpose of this study was to investigate whether FO derived from Sargassum hemiphyllum ameliorates pancreatic β-cell damage and impaired insulin synthesis under diabetic condition. METHODS AND RESULTS: The effects of FO were studied in streptozotocin (STZ)-treated pancreatic β-cell line, NIT-1cells, and mice. The cell apoptosis, protein analyses, histological examination, and pancreatic function assays were performed...
May 11, 2017: Molecular Nutrition & Food Research
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
#7
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/28473214/diabetes-medications-and-cardiovascular-outcomes-in-type-2-diabetes
#8
REVIEW
Cecilia Chi, Jennifer Snaith, Jenny E Gunton
INTRODUCTION: Patients with type 2 diabetes have an increased risk of developing adverse cardiovascular (CV) outcomes. The evidence relating to the effects of glucose-lowering medications on CV outcomes is of variable quality and there are numerous trials ongoing. RESULTS: In this review, we summarise the available literature on CV outcomes of the following diabetes treatments: metformin, the sulfonylureas, acarbose, glucagon-like peptide 1 (GLP1) receptor agonists, dipeptidyl peptidase-4 inhibitors (DPP4i), sodium-glucose co-transporter 2 inhibitors (SGLT2i), thiazolidinediones (TZDs) and insulin...
April 10, 2017: Heart, Lung & Circulation
https://www.readbyqxmd.com/read/28457123/simultaneous-catabolite-identification-and-quantitation-of-large-therapeutic-protein-at-the-intact-level-by-immunoaffinity-capture-liquid-chromatography-high-resolution-mass-spectrometry
#9
Lijuan Kang, Raul C Camacho, Wenyu Li, Katharine D'Aquino, Seohee You, Vanessa Chuo, Naidong Weng, Wenying Jian
As therapeutic recombinant fusion proteins become more widely applicable for the treatment of various types of diseases, there is an increased demand for universal methods such as liquid chromatography (LC)-mass spectrometry (MS) for the determination of their pharmacokinetic properties, particularly their catabolism. The most common approach of analyzing proteins by LC-MS is to digest them into peptides, which can serve as surrogates of the protein. Alternatively, we have developed a novel high-resolution mass spectrometry (HRMS) based approach for analyzing large-molecule proteins at the intact level in biological samples without digestion...
June 6, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28452237/glp-1-and-gip-levels-in-patients-with-hyperthyroidism-the-effect-of-antithyroid-treatment
#10
Duygu Kalkan Cira, Ramazan Sari, Sebahat Ozdem, Nusret Yilmaz, Selen Bozkurt
BACKGROUND: Incretin hormones (glucagon-like peptide-1 [GLP-1] and gastric inhibitory polypeptide [GIP]) may play a role in the development of glucose intolerance and hyperglycemia in patients with hyperthyroidism. OBJECTIVE: We aimed to assess both incretin levels and treatment-induced changes in incretin levels in those with hyperthyroidism. METHODS: A total of 24 subjects (12 with hyperthyroidism and 12 healthy) were enrolled in the study...
April 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28371189/effect-of-glp-1-and-gip-on-c-peptide-secretion-after-glucagon-or-mixed-meal-tests-significance-in-assessing-b-cell-function-in-diabetes
#11
C Guglielmi, R Del Toro, A Lauria, A R Maurizi, S Fallucca, A Cappelli, S Angeletti, J M Lachin, P Pozzilli
BACKGROUND: The aim of the study was to investigate the different B-cell responses after a glucagon stimulation test (GST) versus mixed meal tolerance test (MMTT). METHODS: We conducted GST and MMTT in 10 healthy people (aged 25-40 years) and measured C-peptide, gastric inhibitory peptide (GIP) and glucagon-like peptide-1 (GLP-1) at different time points after the administration of 1 mg i.v. glucagon for GST or a liquid mixed meal for MMTT. RESULTS: The GST stimulated C-peptide showed a mean increase of 147...
March 31, 2017: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/28357772/switch-to-combined-glp1-receptor-agonist-lixisenatide-with-basal-insulin-glargine-in-poorly-controlled-t2dm-patients-with-premixed-insulin-therapy-a-clinical-observation-and-pilot-study-in-nine-patients
#12
Jürgen Harreiter, Lana Kosi-Trebotic, Albert Lukas, Peter Wolf, Yvonne Winhofer, Anton Luger, Alexandra Kautzky-Willer, Michael R Krebs
INTRODUCTION: To prove the feasibility and safety of a conversion to once-daily injected GLP1 agonist (lixisenatide) and long-acting basal insulin analogue (glargine) in patients with T2DM and poorly controlled glycemia previously treated with multiple injections of premixed insulins (iPremix) in an outpatient setting. METHODS: Nine patients with T2DM currently receiving iPremix formulations and poor glycemic control were switched to once-daily injected lixisenatide (Lixi) and basal insulin analogue glargine (iGlar) for a 12-week period...
June 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28338662/diabetes-pancreatic-glp1-is-involved-in-glucose-regulation
#13
Alan Morris
No abstract text is available yet for this article.
May 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/28292762/gpr40-reduces-food-intake-and-body-weight-through-glp-1
#14
Judith N Gorski, Michele J Pachanski, Joel Mane, Christopher W Plummer, Sarah Souza, Brande S Thomas-Fowlkes, Aimie M Ogawa, Adam B Weinglass, Jerry Di Salvo, Boonlert Cheewatrakoolpong, Andrew D Howard, Steven L Colletti, Maria E Trujillo
GPR40 partial agonists lower glucose through the potentiation of glucose-stimulated insulin secretion, which is believed to provide significant glucose lowering without the weight gain or hypoglycemic risk associated with exogenous insulin or glucose independent insulin secretagogues. The class of small molecule GPR40 modulators, known as AgoPAMs (agonist also capable of acting as positive allosteric modulators), differentiate from partial agonists, binding to a distinct site and functioning as full agonists to stimulate the secretion of both insulin and GLP-1 (17)...
March 14, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28285800/perspectives-on-cardiovascular-effects-of-incretin-based-drugs-from-bedside-to-bench-return-trip
#15
Michaela Luconi, Giulia Cantini, Antonio Ceriello, Edoardo Mannucci
Recently, cardiovascular outcome trials with glucose-lowering drugs used in type 2 diabetes mellitus, namely glucagon-like peptide-1 receptor agonists (GLP-1RA), liraglutide and semaglutide, showed a reduction in cardiovascular events, which had not been observed in trials with other incretin-based drugs, such as lixisenatide or with dipeptidyl peptidase-4 inhibitors (DPP4i). Mechanisms underlying the observed cardiovascular differences between DPP4i and GLP1-RA, and across individual GLP1-RA are poorly understood...
March 2, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28271030/high-fidelity-glucagon-creer-mouse-line-generated-by-crispr-cas9-assisted-gene-targeting
#16
Amanda M Ackermann, Jia Zhang, Aryel Heller, Anna Briker, Klaus H Kaestner
OBJECTIVE: α-cells are the second most prominent cell type in pancreatic islets and are responsible for producing glucagon to increase plasma glucose levels in times of fasting. α-cell dysfunction and inappropriate glucagon secretion occur in both type 1 and type 2 diabetes. Thus, there is growing interest in studying both normal function and pathophysiology of α-cells. However, tools to target gene ablation or activation specifically of α-cells have been limited, compared to those available for β-cells...
March 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28270438/menin-and-prmt5-suppress-glp1-receptor-transcript-and-pka-mediated-phosphorylation-of-foxo1-and-creb
#17
Abdul Bari Muhammad, Bowen Xing, Chengyang Liu, Ali Naji, Xiaosong Ma, Rebecca A Simmons, Xianxin Hua
Menin is a scaffold protein that interacts with several epigenetic mediators to regulate gene transcription, and suppresses pancreatic beta cell proliferation. Tamoxifen inducible deletion of multiple endocrine neoplasia type 1 (MEN1) gene, which encodes the protein menin, increases beta cell mass in multiple murine models of diabetes and ameliorates diabetes. Glucagon-like-peptide-1 (GLP1) is another key physiological modulator of beta cell mass and glucose homeostasis. However, it is not clearly understood whether menin crosstalks with GLP1 signaling...
March 7, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28244632/safety-issues-with-glucagon-like-peptide-1-receptor-agonists-pancreatitis-pancreatic-cancer-and-cholelithiasis-data-from-randomized-controlled-trials
#18
Matteo Monami, Besmir Nreu, Alessia Scatena, Barbara Cresci, Francesco Andreozzi, Giorgio Sesti, Edoardo Mannucci
AIM: Glucagon-like peptide 1 receptor agonists (GLP1-RA) have been associated with an increased risk of pancreatitis and pancreatic cancer. Prior meta-analyses of randomized controlled trials failed to show any significant increase of risk; however, those meta-analyses did not include the recently published cardiovascular outcome trials (CVOT) with GLP1-RA, which provide a substantial additional body of data. The aim of the present meta-analysis is to assess the effect of GLP1-RA on pancreatitis, pancreatic cancers and cholelithiasis...
February 28, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28213092/prediction-of-thyroid-c-cell-carcinogenicity-after-chronic-administration-of-glp1-r-agonists-in-rodents
#19
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...
April 1, 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
#20
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
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