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GLP-1 Analogues

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https://www.readbyqxmd.com/read/29350569/practice-pearl-liraglutide-and-cardiovascular-and-renal-events-in-type-2-diabetes
#1
Robert Guthrie
Review of: Marso S, Daniels G, Brown-Frandsen K, et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2016; 375: 311-322. Mann J, Orsted D, Brown-Frandsen K, et al. Liraglutide and Renal Outcomes in Type 2 Diabetes. N Engl J Med 2017; 377: 839-848. This comprehensive research project, LEADER, led to two reports, one focusing on the effect of liraglutide on cardiovascular events, and the second one reporting on the renal effects on the same study population. The study group included 9340 patients with type 2 diabetes...
January 19, 2018: Postgraduate Medicine
https://www.readbyqxmd.com/read/29344656/liraglutide-suppresses-proliferation-and-induces-adipogenic-differentiation-of-3t3-l1-cells-via-the-hippo-yap-signaling-pathway
#2
Yongmei Li, Jianying Du, Endong Zhu, Juanjuan Zhang, Jie Han, Wei Zhao, Bei Sun, Derun Tian
Liraglutide, as a glucagon-like peptide‑1 analogue, is used to treat type 2 diabetes mellitus and obesity. Previous findings have demonstrated the effects of liraglutide on adipogenesis; however, the underlying mechanism involved in this process remains to be elucidated. In the present study, to certify the effect of liraglutide on adipogenesis and explore the possible underlying mechanism involved in this process, preadipocyte 3T3‑L1 cells were cultured in adipocyte‑inducing medium and treated with liraglutide...
January 16, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29337226/glp-1-signaling-and-alcohol-mediated-behaviors-preclinical-and-clinical-evidence
#3
REVIEW
Elisabet Jerlhag
Alcohol addiction, affecting approximately four percent of the population, contributes significantly to the global burden of diseases and is a substantial cost to the society. The neurochemical mechanisms regulating alcohol mediated behaviors is complex and in more recent years a new physiological role of the gut-brain peptides, traditionally known to regulate appetite and food intake, have been suggested. Indeed, regulators of alcohol-mediated behaviors. One of these gut-brain peptides is the annorexigenic peptide glucagon-like peptide-1 (GLP-1), Preclinical studies show that GLP-1 receptor activation, either by GLP-1 or analogues, attenuate the ability of alcohol to activate the mesolimbic dopamine system as well as decrease alcohol consumption and operant self-administration...
January 11, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29331730/exenatide-exerts-cognitive-effects-by-modulating-the-bdnf-trkb-neurotrophic-axis-in-adult-mice
#4
Manuela Bomba, Alberto Granzotto, Vanessa Castelli, Noemi Massetti, Elena Silvestri, Lorella M T Canzoniero, Annamaria Cimini, Stefano L Sensi
Modulation of insulin-dependent signaling is emerging as a valuable therapeutic tool to target neurodegeneration. In the brain, the activation of insulin receptors promotes cell growth, neuronal repair, and protection. Altered brain insulin signaling participates in the cognitive decline seen in Alzheimer's disease patients and the aging brain. Glucagon-like peptide-1 (GLP-1) regulates insulin secretion and, along with GLP-1 analogues, enhances neurotrophic signaling and counteracts cognitive deficits in preclinical models of neurodegeneration...
December 19, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29310645/effects-of-6-month-treatment-with-the-glucagon-like-peptide-1-analogue-liraglutide-on-arterial-stiffness-left-ventricular-myocardial-deformation-and-oxidative-stress-in-subjects-with-newly-diagnosed-type-2-diabetes
#5
Vaia Lambadiari, George Pavlidis, Foteini Kousathana, Maria Varoudi, Dimitrios Vlastos, Eirini Maratou, Dimitrios Georgiou, Ioanna Andreadou, John Parissis, Helen Triantafyllidi, John Lekakis, Efstathios Iliodromitis, George Dimitriadis, Ignatios Ikonomidis
BACKGROUND: Incretin-based therapies are used in the treatment of type 2 diabetes mellitus (T2DM) and obesity. We investigated the changes in arterial stiffness and left ventricular (LV) myocardial deformation after 6-month treatment with the GLP-1 analogue liraglutide in subjects with newly diagnosed T2DM. METHODS: We randomized 60 patients with newly diagnosed and treatment-naive T2DM to receive either liraglutide (n = 30) or metformin (n = 30) for 6 months...
January 8, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29286061/cardioprotection-by-exenatide-a-novel-mechanism-via-improving-mitochondrial-function-involving-the-glp-1-receptor-camp-pka-pathway
#6
Guanglei Chang, Jian Liu, Shu Qin, Youqin Jiang, Peng Zhang, Hui Yu, Kai Lu, Nan Zhang, Li Cao, Ying Wang, Yong Li, Dongying Zhang
Accumulating evidence suggests that glucagon-like peptide-1 (GLP-1) and its analogues exert cardioprotective effects via modulating cardiomyocyte metabolism. Mitochondria play a pivotal role in the regulation of cell metabolism. It was hypothesized that treatment with exenatide, a GLP-1 analogue, may exert cardioprotective effects by improving mitochondrial function in an in vitro model of hypoxia/reoxygenation (H/R). H9c2 cells were employed to establish an in vitro model of H/R. Exenatide was added to the cells for 30 min prior to exposure to hypoxia...
December 12, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29284659/a-targeted-rnai-screen-identifies-endocytic-trafficking-factors-that-control-glp-1-receptor-signaling-in-pancreatic-beta-cells
#7
Teresa Buenaventura, Nisha Kanda, Phoebe C Douzenis, Ben Jones, Stephen R Bloom, Pauline Chabosseau, Ivan R Corrêa, Domenico Bosco, Lorenzo Piemonti, Piero Marchetti, Paul R Johnson, Am James Shapiro, Guy A Rutter, Alejandra Tomas
The GLP-1 receptor (GLP-1R) is a key target for type 2 diabetes (T2D) treatment. Since endocytic trafficking of agonist-bound receptors is one of the most important routes for regulation of receptor signaling, a better understanding of this process may facilitate the development of new T2D therapeutic strategies. Here, we have screened 29 proteins with known functions in G protein-coupled receptor trafficking for their role in GLP-1R potentiation of insulin secretion in pancreatic beta cells. We identify five (clathrin, dynamin1, AP2, SNX27 and SNX1) that increase and four (HIP1, HIP14, GASP-1 and Nedd4) that decrease insulin secretion from murine insulinoma MIN6B1 cells in response to the GLP-1 analogue exendin-4...
December 28, 2017: Diabetes
https://www.readbyqxmd.com/read/29283894/incretin-based-drugs-and-the-incidence-of-colorectal-cancer-in-patients-with-type-2-diabetes
#8
Devin Abrahami, Hui Yin, Oriana H Y Yu, Michael N Pollak, Laurent Azoulay
BACKGROUND: Evidence on the safety of the incretin-based drugs (glucagon-like peptide-1 [GLP-1] analogues and dipeptidyl peptidase-4 [DPP-4] inhibitors) with respect to colorectal cancer is contradictory. The objective of this study was to determine whether use of incretin-based drugs is associated with risk of incident colorectal cancer in patients with type 2 diabetes. METHODS: Using data from the United Kingdom Clinical Practice Research Datalink, we identified a cohort of 112,040 patients newly treated with antidiabetic drugs between 1 January 2007 and 31 March 2015...
December 26, 2017: Epidemiology
https://www.readbyqxmd.com/read/29283509/exenatide-exhibits-anti-inflammatory-properties-and-modulates-endothelial-response-to-tumor-necrosis-factor-%C3%AE-mediated-activation
#9
Wojciech Garczorz, Enrique Gallego-Colon, Agnieszka Kosowska, Agnieszka Kłych-Ratuszny, Michał Woźniak, Wiesław Marcol, K J Niesner, Tomasz Francuz
INTRODUCTION: Cardiovascular disease is the main cause of mortality and morbidity in the industrialized world. Incretin mimetic compounds such as exenatide are currently used in the treatment of type 2 diabetes. AIMS: We investigated the effects of incretin drugs on apoptosis, adhesion molecule expression, and concentration of extracellular matrix (ECM) metalloproteinases under inflammatory conditions within the context of atherosclerotic plaque formation of both human coronary artery endothelial cells (hCAECs) and human aortic endothelial cells (hAoECs)...
December 28, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/29274367/the-effects-of-incretin-hormones-on-cerebral-glucose-metabolism-in-health-and-disease
#10
REVIEW
Malin Nilsson, Albert Gjedde, Birgitte Brock, Michael Gejl, Jørgen Rungby
Incretin hormones, notably glucagon-like peptide-1 (GLP-1), are gluco-regulatory hormones with pleiotropic effects also in the central nervous system. Apart from a local production of GLP-1, systemic administration of the hormone has been shown to influence a number of cerebral pathologies, including neuroinflammation. Given the brains massive dependence on glucose as its major fuel, we here review the mechanistics of cerebral glucose transport and metabolism, focusing on the deleterious effects of both hypo- and hyperglycaemia...
December 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29259802/the-effect-of-the-glp-1-analogue-exenatide-on-functional-connectivity-within-an-nts-based-network-in-women-with-and-without-obesity
#11
K Coveleskie, L A Kilpatrick, A Gupta, J Stains, L Connolly, J S Labus, C Sanmiguel, E A Mayer
Objective: The differential effect of GLP-1 agonist Exenatide on functional connectivity of the nucleus tractus solitaries (NTS), a key region associated with homeostasis, and on appetite-related behaviours was investigated in women with normal weight compared with women with obesity. Methods: Following an 8-h fast, 19 female subjects (11 lean, 8 obese) participated in a 2-d double blind crossover study. Subjects underwent functional magnetic resonance imaging at fast and 30-min post subcutaneous injection of 5 μg of Exenatide or placebo...
December 2017: Obesity Science & Practice
https://www.readbyqxmd.com/read/29247356/current-and-future-pharmacological-therapies-for-nafld-nash
#12
REVIEW
Yoshio Sumida, Masashi Yoneda
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and there is no approved pharmacotherapy. The efficacy of vitamin E and pioglitazone has been established in nonalcoholic steatohepatitis (NASH), a progressive form of NAFLD. GLP-1RA and SGLT2 inhibitors, which are currently approved for use in diabetes, have shown early efficacy in NASH, and also have beneficial cardiovascular or renal effects. Innovative NASH therapies include four main pathways. The first approach is targeting hepatic fat accumulation...
December 16, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/29229616/glutamine-elicited-secretion-of-glucagon-like-peptide-1-glp-1-is-governed-by-an-activated-glutamate-dehydrogenase
#13
Lotta E Andersson, Liliya Shcherbina, Mahmoud Al-Majdoub, Neelanjan Vishnu, Claudia Balderas Arroyo, Jonathan Aste Carrara, Claes B Wollheim, Malin Fex, Hindrik Mulder, Nils Wierup, Peter Spégel
Glucagon-like peptide-1 (GLP-1), secreted from intestinal L-cells, glucose-dependently stimulates insulin secretion from beta-cells. This glucose-dependence prevents hypoglycemia, rendering GLP-1 analogues a useful and safe treatment modality in type-2 diabetes. While the amino acid glutamine is a potent elicitor of GLP-1 secretion, the responsible mechanism remains unclear.We investigated how GLP-1 secretion is metabolically coupled in L-cells (GLUTag) and in vivo in mice, using the insulin-secreting cell-line INS-1 832/13 as reference...
December 11, 2017: Diabetes
https://www.readbyqxmd.com/read/29226618/enteroinsular-hormones-in-two-siblings-with-donohue-syndrome-and-complete-leptin-deficiency
#14
M Güemes, S A Rahman, P Shah, K Hussain
The main biochemical hallmark of the rare and lethal condition of Donohue syndrome (DS) is hyperinsulinemia. The roles of the gut and other pancreatic hormones involved in glucose metabolism, satiety and energy expenditure have not been previously reported in DS. Two siblings with genetically confirmed DS and extremely low weight underwent a mixed meal (MM) test where pancreatic hormones insulin, C-peptide, glucagon, active amylin, pancreatic polypeptide (PP) as well as gut hormones active glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), ghrelin, peptide YY (PYY) and leptin were analyzed using a Multiplex assay...
December 11, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/29225158/exendin-4-partly-ameliorates-of-hyperglycemia-mediated-tissue-damage-in-lungs-of-streptozotocin-induced-diabetic-mice
#15
Fusun Oztay, Serap Sancar Bas, Selda Gezginci-Oktayoglu, Merve Ercin, Sehnaz Bolkent
Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion, and plays anti-inflammatory role in atherosclerosis, and has surfactant-releasing effects in lungs. GLP-1 analogues are used in diabetes therapy. This is the first study to investigate the effects of exendin-4, a GLP-1 receptor agonist, on lung injury in diabetic mice. BALB/c male mice were divided into four groups. The first group was given only citrate buffer, the second group was given only exendin-4, the third group was given only streptozotocin (STZ), and the fourth group was given both exendin-4 and STZ...
December 7, 2017: Peptides
https://www.readbyqxmd.com/read/29203510/mechanisms-to-elevate-endogenous-glucagon-like-peptide-1-glp-1-beyond-injectable-glp-1-analogues-and-metabolic-surgery
#16
Daniel A Briere, Ana B Bueno, Ellen J Gunn, M Dodson Michael, Kyle W Sloop
Therapeutic engineering of glucagon-like peptide-1 (GLP-1) has enabled development of new medicines to treat type 2 diabetes mellitus. These injectable analogues achieve robust glycemic control by increasing concentrations of 'GLP-1 equivalents' (∼50 pM). Similar levels of endogenous GLP-1 occur following gastric bypass surgery, and mechanistic studies indicate glucose lowering by these procedures is driven by GLP-1. Therefore, due to the remarkable signaling and secretory capacity of the GLP-1 system, we sought to discover mechanisms that raise GLP-1 pharmacologically...
December 4, 2017: Diabetes
https://www.readbyqxmd.com/read/29177486/glucagon-like-peptide-1-inhibits-prandial-gastrointestinal-motility-through-myenteric-neuronal-mechanisms-in-humans
#17
Md Abdul Halim, Marie Degerblad, Magnus Sundbom, Urban Karlbom, Jens Juul Holst, Dominic-Luc Webb, Per M Hellström
Context: Glucagon-like peptide-1 (GLP-1) secretion from L-cells and postprandial inhibition of gastrointestinal motility. Objective: Investigate whether physiological plasma concentrations of GLP-1 can inhibit human postprandial gastrointestinal motility; determine target mechanism of GLP-1 and analogue ROSE-010 action. Design: Single-blind parallel study. Setting: University research laboratory. Participants: Healthy volunteers investigated with antroduodenojejunal manometry...
November 21, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29171021/xenopus-glp-1-derived-and-pegylated-glp-1-receptor-agonists-long-acting-hypoglycemic-and-insulinotropic-activities-with-potential-therapeutic-utilities
#18
Jing Han, Yingying Fei, Feng Zhou, Xinyu Chen, Ying Zhang, Lin Liu, Junjie Fu
BACKGROUND AND PURPOSE: Incretin-based therapies based on glucagon-like peptide-1 (GLP-1) receptor agonists are effective methods for treating type 2 diabetes. Numerous research efforts are focused on the development of long-acting GLP-1 receptor agonists. However, all GLP-1 receptor agonists in clinical use or in clinical development are based on human GLP-1 or Gila GLP-1. We previously identified xGLP-1B as a potent GLP-1 receptor agonist based on Xenopus GLP-1. EXPERIMENTAL APPROACH: To further modify the structure of xGLP-1B, alanine scanning was performed to study the structure-activity relationship of xGLP-1B...
November 24, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29158344/effects-of-walking-in-water-on-gut-hormone-concentrations-and-appetite-comparison-with-walking-on-land
#19
Shin-Ya Ueda, Hidehiro Nakahara, Eriko Kawai, Tatsuya Usui, Shintaro Tsuji, Tadayoshi Miyamoto
The effects of water exercise on gut hormone concentrations and appetite currently remain unclear. The aim of the present study was to investigate the effects of treadmill walking in water on gut hormone concentrations and appetite. Thirteen men (mean ± s.d. age: 21.6 ± 2.2 years, body mass index: 22.7 ± 2.8 kg/m2, peak oxygen uptake (VO2peak): 49.8 ± 7.8 mL/kg per min) participated in the walking in water and on land challenge. During the study period, ratings of subjective feelings of hunger, fullness, satiety and motivation to eat were reported on a 100-mm visual analog scale...
January 2018: Endocrine Connections
https://www.readbyqxmd.com/read/29130686/thioamide-substitution-selectively-modulates-proteolysis-and-receptor-activity-of-therapeutic-peptide-hormones
#20
Xing Chen, Elizabeth G Mietlicki-Baase, Taylor M Barrett, Lauren E McGrath, Kieran Koch-Laskowski, John J Ferrie, Matthew R Hayes, E James Petersson
Peptide hormones are attractive as injectable therapeutics and imaging agents, but they often require extensive modification by mutagenesis and/or chemical synthesis to prevent rapid in vivo degradation. Alternatively, the single-atom, O-to-S modification of peptide backbone thioamidation has the potential to selectively perturb interactions with proteases while preserving interactions with other proteins, such as target receptors. Here, we use the validated diabetes therapeutic, glucagon-like peptide-1 (GLP-1), and the target of clinical investigation, gastric inhibitory polypeptide (GIP), as proof-of-principle peptides to demonstrate the value of thioamide substitution...
November 13, 2017: Journal of the American Chemical Society
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