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https://www.readbyqxmd.com/read/28105738/glucagon-like-peptide-1-agonists-and-risk-of-acute-pancreatitis-in-patients-with-type-2-diabetes
#1
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/28103783/understanding-corticotropin-releasing-factor-receptor-crfr-activation-using-structural-models
#2
Arnau Cordomi, George Liapakis, Minos Timotheos Matsoukas
The corticotropin-releasing factor type 1 and 2 receptors (CRF1R and CRF2R) belong to the secretin-like family, also known as class B1, of G protein-coupled receptors (GPCRs). Several endogenous hormones mediate their responses through the CRF receptors, such as CRF and the urocortins. The structures for the N-terminus extracellular domain of both CRF1R and CRF2R in complex with peptidic ligands were released a few years ago and permitted the study of hormone binding to the orthosteric binding site. It was not until more recently, when the crystal structure of the transmembrane domain of human CRF1R in its inactive state bound to an allosteric antagonist became available...
January 10, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28102093/cardiovascular-safety-and-benefits-of-glp-1-receptor-agonists
#3
Niels B Dalsgaard, Andreas Brønden, Tina Vilsbøll, Filip K Knop
Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) constitute a class of drugs for the treatment of type 2 diabetes, and currently, six different GLP-1RAs are approved. Besides improving glycemic control, the GLP-1RAs have other beneficial effects such as weight loss and a low risk of hypoglycemia. Treatment with the GLP-1RA lixisenatide has been shown to be safe in patients with type 2 diabetes and recent acute coronary syndrome. Furthermore, liraglutide and semaglutide have been shown to reduce cardiovascular (CV) disease (CVD) risk in type 2 diabetes patients with established and/or high risk of CVD...
January 19, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28098139/appetite-responses-to-high-fat-meals-or-diets-of-varying-fatty-acid-composition-a-comprehensive-review
#4
REVIEW
S Kaviani, J A Cooper
Dietary fatty acids (FA) act as signaling molecules with diverse effects on physiologic function. The aim of this article is to review and summarize the clinical human studies in the literature on how dietary FA composition in meals and diets affects hunger and satiety signaling in the body. Studies examining FA saturation (monounsaturated (MUFA), saturated or polyunsaturated (PUFA) FAs) or FA chain length from high-fat meals/diets were included. Measures of appetite included visual analog scale (VAS) questionnaires, appetite hormones (Cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), gastric insulinotropic polypeptide gastric inhibitory peptide (GIP), ghrelin, leptin, insulin) and/or energy intake (EI) data...
January 18, 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28097390/a-role-of-plc-pkc-dependent-pathway-in-glp-1-stimulated-insulin-secretion
#5
REVIEW
Makoto Shigeto, Chae Young Cha, Patrik Rorsman, Kohei Kaku
Glucagon-like peptide-1 (GLP-1) is an endogenous glucose-lowering hormone and GLP-1 receptor agonists are currently being used as antidiabetic drugs clinically. The canonical signalling pathway (including cAMP, Epac2, protein kinase A (PKA) and KATP channels) is almost universally accepted as the main mechanism of GLP-1-stimulated insulin secretion. This belief is based on in vitro studies that used nanomolar (1-100 nM) concentrations of GLP-1. Recently, it was found that the physiological concentrations (1-10 pM) of GLP-1 also stimulate insulin secretion from isolated islets, induce membrane depolarization and increase of intracellular [Ca(2+)] in isolated β cells/pancreatic islets...
January 17, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28096522/control-of-food-intake-by-gastrointestinal-peptides-mechanisms-of-action-and-possible-modulation-in-the-treatment-of-obesity
#6
REVIEW
Philip Prinz, Andreas Stengel
This review focuses on the control of appetite by food intake-regulatory peptides secreted from the gastrointestinal tract, namely cholecystokinin, glucagon-like peptide 1, peptide YY, ghrelin, and the recently discovered nesfatin-1 via the gut-brain axis. Additionally, we describe the impact of external factors such as intake of different nutrients or stress on the secretion of gastrointestinal peptides. Finally, we highlight possible conservative-physical activity and pharmacotherapy-treatment strategies for obesity as well as surgical techniques such as deep brain stimulation and bariatric surgery also altering these peptidergic pathways...
January 17, 2017: Journal of Neurogastroenterology and Motility
https://www.readbyqxmd.com/read/28095318/interoceptive-modulation-of-neuroendocrine-emotional-and-hypophagic-responses-to-stress
#7
REVIEW
James W Maniscalco, Linda Rinaman
Periods of caloric deficit substantially attenuate many centrally mediated responses to acute stress, including neural drive to the hypothalamic-pituitary-adrenal (HPA) axis, anxiety-like behavior, and stress-induced suppression of food intake (i.e., stress hypophagia). It is posited that this stress response plasticity supports food foraging and promotes intake during periods of negative energy balance, even in the face of other internal or external threats, thereby increasing the likelihood that energy stores are repleted...
January 14, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28091894/mechanisms-of-action-of-surgical-interventions-on-weight-related-diseases-the-potential-role-of-bile-acids
#8
REVIEW
Mohsen Mazidi, Pedro Paulo P de Caravatto, John R Speakman, Ricardo V Cohen
Surgical interventions for weight-related diseases (SWRD) may have substantial and sustainable effect on weight reduction, also leading to a higher remission rate of type 2 diabetes (T2D) mellitus than any other medical treatment or lifestyle intervention. The resolution of T2D after Roux-en-Y gastric bypass (RYGB) typically occurs too quickly to be accounted for by weight loss alone, suggesting that these operations have a direct impact on glucose homeostasis. The mechanisms underlying these beneficial effects however remain unclear...
January 14, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28086882/differential-effects-of-glucagon-like-peptide-1-receptor-agonists-on-heart-rate
#9
REVIEW
Martin Lorenz, Francesca Lawson, David Owens, Denis Raccah, Christine Roy-Duval, Anne Lehmann, Riccardo Perfetti, Lawrence Blonde
While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are known to increase heart rate (HR), it is insufficiently recognized that the extent varies greatly between the various agonists and is affected by the assessment methods employed. Here we review published data from 24-h time-averaged HR monitoring in healthy individuals and subjects with type 2 diabetes mellitus (T2DM) treated with either short-acting GLP-1 RAs, lixisenatide or exenatide, or long-acting GLP-1 RAs, exenatide LAR, liraglutide, albiglutide, or dulaglutide (N = 1112; active-treatment arms)...
January 13, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28076485/glp-2-a-poorly-understood-mediator-enrolled-in-various-bariatric-metabolic-surgery-related-pathophysiologic-mechanisms
#10
Everton Cazzo, Martinho Antonio Gestic, Murillo Pimentel Utrini, Felipe David Mendonça Chaim, Bruno Geloneze, José Carlos Pareja, Elinton Adami Chaim, Daniéla Oliveira Magro
Introduction: Glucagon-like peptide-2 (GLP-2) is a gastrointestinal hormone whose effects are predominantly trophic on the intestinal mucosa. Aim: Critically evaluate the current literature on the influence of bariatric/metabolic surgery on the levels of GLP-2 and its potential clinical implications. Method: s: Narrative review through online research on the databases Medline and Lilacs. There were six prospective human studies, two cross-sectional human studies, and three experimental animal studies selected...
November 2016: Arquivos Brasileiros de Cirurgia Digestiva: ABCD, Brazilian Archives of Digestive Surgery
https://www.readbyqxmd.com/read/28074747/liraglutide-a-glucagon-like-peptide-1-agonist-for-chronic-weight-management
#11
Kendra R Manigault, Maria Miller Thurston
OBJECTIVE: To review the efficacy and safety of liraglutide 3.0 mg for weight loss. DATA SOURCE: A literature search was performed using PubMed and MEDLINE from 2000 to 2016. The following key terms were used alone or in combination: glucagon-like peptide-1 agonist, liraglutide, obesity, overweight, and weight loss. Additional supporting literature was identified utilizing the reference lists of the preceding articles. STUDY SELECTION: Analyzed studies were published in English and investigated use of liraglutide and its impact on weight loss...
December 1, 2016: Consultant Pharmacist: the Journal of the American Society of Consultant Pharmacists
https://www.readbyqxmd.com/read/28065744/efficacy-and-safety-of-glucagon-like-peptide-1-receptor-agonists-in-non-alcoholic-fatty-liver-disease-a-systematic-review-and-meta-analysis
#12
Yajie Dong, Qingguo Lv, Sheyu Li, Yuan Wu, Ling Li, Juan Li, Fang Zhang, Xin Sun, Nanwei Tong
BACKGROUND AND OBJECTIVE: New drugs are urgently needed for the treatment of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The aim of this meta-analysis was to evaluate the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in NAFLD/NASH. METHODS: We searched the MEDLINE, Embase, and Cochrane Library Central to identify randomized controlled trials (RCTs) and observational studies that compared GLP-1RAs with a control treatment or baseline values with respect to efficacy and safety in patients with NAFLD/NASH...
January 5, 2017: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/28040864/glp-1-receptor-independent-pathways-emerging-beneficial-effects-of-glp-1-breakdown-products
#13
REVIEW
Valeria Guglielmi, Paolo Sbraccia
The glucagon-like peptide-1 (GLP-1) axis has emerged as a major therapeutic target for the treatment of type 2 diabetes and, recently, of obesity. The insulinotropic activity of the native incretin hormone GLP-1(7-36)amide, which is mainly exerted through a unique G protein-coupled receptor (GLP-1R), is terminated via enzymatic cleavage by dipeptidyl peptidase-IV that generates a C-terminal GLP-1 metabolite GLP-1(9-36)amide, the major circulating form in plasma. GLP-1(28-36)amide and GLP-1(32-36)amide are further cleavage products derived from GLP-1(7-36)amide and GLP-1(9-36)amide by the action of a neutral endopeptidase known as neprilysin...
December 31, 2016: Eating and Weight Disorders: EWD
https://www.readbyqxmd.com/read/28019064/novel-antidiabetic-medications-for-nonalcoholic-fatty-liver-disease-with-type-2-diabetes
#14
REVIEW
Yoshio Sumida, Yuya Seko, Masashi Yoneda
Liver related diseases are the leading causes of death in type 2 diabetes mellitus (T2DM) in Japan. T2DM is closely associated with nonalcoholic fatty liver disease (NAFLD) which is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma (HCC) and hepatic failure. NASH can be called "diabetic hepatopathy". There are no established pharmacotherapies for NAFLD/NASH patients with T2DM. Although metformin is established as the first-line therapy for T2DM, given its relative safety and beneficial effects on glycosylated hemoglobin (HbA1c), weight, and cardiovascular mortality, this agent is not recommended as specific therapy for NASH/NAFLD due to no clinical evidences...
December 26, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28003328/ghrelin-cck-glp-1-and-pyy-3-36-secretory-controls-and-physiological-roles-in-eating-and-glycemia-in-health-obesity-and-after-rygb
#15
REVIEW
Robert E Steinert, Christine Feinle-Bisset, Lori Asarian, Michael Horowitz, Christoph Beglinger, Nori Geary
The efficacy of Roux-en-Y gastric-bypass (RYGB) and other bariatric surgeries in the management of obesity and type 2 diabetes mellitus and novel developments in gastrointestinal (GI) endocrinology have renewed interest in the roles of GI hormones in the control of eating, meal-related glycemia, and obesity. Here we review the nutrient-sensing mechanisms that control the secretion of four of these hormones, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide tyrosine tyrosine [PYY(3-36)], and their contributions to the controls of GI motor function, food intake, and meal-related increases in glycemia in healthy-weight and obese persons, as well as in RYGB patients...
January 2017: Physiological Reviews
https://www.readbyqxmd.com/read/27995402/does-the-ileal-brake-contribute-to-delayed-gastric-emptying-after-pancreatoduodenectomy
#16
REVIEW
Savio G Barreto, John A Windsor
Delayed gastric emptying (DGE) represents a significant cause for morbidity following pancreatoduodenectomy (PD). At a time when no specific and universally effective therapy exists to treat these patients, elucidating other potential (preventable or treatable) mechanisms for DGE is important. The aim of the manuscript was to test the hypothesis that ileal brake contributes to DGE in PD patients receiving jejunal tube feeding by systematically reviewing experimental and clinical literature. A series of clinically relevant questions were framed related to the potential role of the ileal brake in development of DGE post-PD and formed the basis of targeted literature searches...
December 19, 2016: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/27990172/nutritional-modulation-of-endogenous-glucagon-like-peptide-1-secretion-a-review
#17
REVIEW
Alexandra M Bodnaruc, Denis Prud'homme, Rosanne Blanchet, Isabelle Giroux
BACKGROUND: The positive influences of glucagon-like peptide-1 (GLP-1) on blood glucose homeostasis, appetite sensations, and food intake provide a strong rationale for its therapeutic potential in the nutritional management of obesity and type 2 diabetes. AIM: To summarize GLP-1 physiology and the nutritional modulation of its secretion in the context of obesity and type 2 diabetes management. FINDINGS: GLP-1 is mainly synthesized and secreted by enteroendocrine L-cells of the gastrointestinal tract...
2016: Nutrition & Metabolism
https://www.readbyqxmd.com/read/27981757/efficacy-and-safety-of-glucagon-like-peptide-1-receptor-agonists-in-type-2-diabetes-systematic-review-and-mixed-treatment-comparison-analysis
#18
Zin Z Htike, Francesco Zaccardi, Dimitris Papamargaritis, David R Webb, Kamlesh Khunti, Melanie J Davies
AIMS: To compare efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in subjects with type 2 diabetes MATERIALS AND METHODS: We electronically searched, up to June 3(rd) , 2016, published randomised clinical trials lasting between 24 and 32 weeks and comparing a GLP-1RA (albiglutide, dulaglutide, twice-daily (EBID) and once-weekly exenatide, liraglutide, lixisenatide, semaglutide, and taspoglutide) with placebo or another GLP-1RA. Data on cardiometabolic and safety outcomes were analysed using a mixed-treatment comparison meta-analysis RESULTS: 34 trials (14464 participants) met the inclusion criteria; no published data for semaglutide were available...
December 15, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27976513/what-next-after-basal-insulin-treatment-intensification-with-lixisenatide-in-asian-patients-with-type-2-diabetes-mellitus
#19
REVIEW
Wing Bun Chan, Andrea Luk, Wing Sun Chow, Vincent Tok Fai Yeung
There is increasing evidence that the pathophyisology of type 2 diabetes mellitus (T2DM) in Asian patients differs from that seen in western patients, with early phase insulin deficiencies, increased postprandial glucose excursions, and increased sensitivity to insulin. Asian patients may also experience higher rates of gastrointestinal adverse events associated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as nausea and vomiting, compared with their western counterparts. These factors should be taken into consideration when selecting therapy for basal insulin treatment intensification in Asian patients...
December 15, 2016: Journal of Diabetes
https://www.readbyqxmd.com/read/27924636/safety-and-tolerability-of-glucagon-like-peptide-1-receptor-agonists-unresolved-and-emerging-issues
#20
Denis Raccah
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a mainstay of treatment options for type 2 diabetes. They contribute to lowering blood glucose levels, generally have a favorable tolerability profile, and can be used alone or in combination with other antidiabetic agents. Based on the duration of their effects, GLP-1 RAs can be divided into two classes: short-acting and long-acting. Differences exist between these sub-classes, and between each drug, in terms of pharmacokinetic and pharmacodynamic profiles...
December 11, 2016: Expert Opinion on Drug Safety
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