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Glucagon-like peptide

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https://www.readbyqxmd.com/read/29223528/glp-1-receptor-agonists-downregulate-aberrant-gnt-iii-expression-in-alzheimer-s-disease-models-through-the-akt-gsk-3%C3%AE-%C3%AE-catenin-signaling
#1
Ying Wang, Song Chen, Zheng Xu, Suting Chen, Wenbing Yao, Xiangdong Gao
Alterations of glycoprotein glycans contribute to a wide variety of diseases. Bisecting N-acetylglucosamine (GlcNAc) levels increased in the cerebrospinal fluid of most Alzheimer's disease (AD) patients, and the mRNA levels of N-acetylglucosaminyltransferase III (GnT-III), a glycosyltransferase responsible for synthesizing a bisecting GlcNAc residue, were found highly expressed in the brains of AD patients. In our previous studies, glucagon-like peptide-1 (GLP-1) and its mimetics showed neuroprotective effects...
December 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29221794/glp-1-action-in-the-mouse-bed-nucleus-of-the-stria-terminalis
#2
Diana L Williams, Nicole A Lilly, Ian J Edwards, Pallas Yao, James E Richards, Stefan Trapp
Glucagon-like peptide-1 (GLP-1) injected into the brain reduces food intake. Similarly, activation of preproglucagon (PPG) cells in the hindbrain which synthesize GLP-1, reduces food intake. However, it is far from clear whether this happens because of satiety, nausea, reduced reward, or even stress. Here we explore the role of the bed nucleus of the stria terminalis (BNST), an area involved in feeding control as well as stress responses, in GLP-1 responses. Using cre-expressing mice we visualized projections of NTS PPG neurons and GLP-1R-expressing BNST cells with AAV-driven Channelrhodopsin-YFP expression...
December 5, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29221659/cardiovascular-outcomes-with-glucagon-like-peptide-1-receptor-agonists-in-patients-with-type-2-diabetes-a-meta-analysis
#3
M Angelyn Bethel, Rishi A Patel, Peter Merrill, Yuliya Lokhnygina, John B Buse, Robert J Mentz, Neha J Pagidipati, Juliana C Chan, Stephanie M Gustavson, Nayyar Iqbal, Aldo P Maggioni, Peter Öhman, Neil R Poulter, Ambady Ramachandran, Bernard Zinman, Adrian F Hernandez, Rury R Holman
BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists are effective glucose-lowering drugs. Findings from cardiovascular outcome trials showed cardiovascular safety of GLP-1 receptor agonists, but results for cardiovascular efficacy were varied. We aimed to examine overall cardiovascular efficacy for lixisenatide, liraglutide, semaglutide, and extended-release exenatide. METHODS: In this systematic review and meta-analysis, we analysed data from eligible trials that assessed the safety and efficacy of GLP-1 receptor agonists compared with placebo in adult patients (aged 18 years or older) with type 2 diabetes and had a primary outcome including, but not limited to, cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke...
December 5, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/29220092/dose-rectification-of-an-unbalance-between-dpp4-and-glp-1-ameliorates-chronic-stress-related-vascular-aging-and-atherosclerosis
#4
Xian Wu Cheng, Megumi Narisawa, Enze Jin, Chenglin Yu, Wenhu Xu, Limei Piao
Exposure to psychosocial stress is a risk factor for cardiovascular disease, including vascular aging and regeneration. Dipeptidyl peptidase-4 (DPP-4) exerts many physiological and pharmacological functions by regulating its extremely abundant substrates [e.g., glucagon-like peptide-1 (GLP-1), stromal cell-derived factor-1α/ C-X-C chemokine receptor type-4, etc.]. Over the past decade, emerging data revealed unexpected roles for DPP-4 and GLP-1 in intracellular signaling, oxidative stress production, lipid metabolism, cell apoptosis, immune activation, insulin resistance, and inflammation...
December 8, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29218595/quantitative-testing-of-prescriber-knowledge-regarding-the-risks-and-safe-use-of-albiglutide
#5
Carol Koro, Janet Pientka, Veronica Bainbridge, Natalie O'Donnell, Monika Stender, Annette Stemhagen
BACKGROUND: The risk of pancreatitis and potential risk of medullary thyroid carcinoma associated with glucagon-like peptide-1 receptor agonists prompted the US Food and Drug Administration to require a Risk Evaluation and Mitigation Strategy for albiglutide, including education for prescribers and subsequent assessment of their knowledge of the risks and safe use of albiglutide via a quantitative survey. OBJECTIVE: The objective of this study was to assess prescribers' knowledge of the risks related to medullary thyroid carcinoma, pancreatitis, and the appropriate patient population for albiglutide...
December 7, 2017: Drugs—Real World Outcomes
https://www.readbyqxmd.com/read/29217412/glucagon-like-peptide-1-receptor-agonists-reduced-the-low-density-lipoprotein-cholesterol-in-japanese-patients-with-type-ii-diabetes-mellitus-treated-with-statins
#6
Yukiko Hasegawa, Mika Hori, Tomoko Nakagami, Mariko Harada-Shiba, Yasuko Uchigata
BACKGROUND: Patients with type II diabetes mellitus (T2DM) often have hypercholesterolemia, and their serum low-density lipoprotein cholesterol (LDL-C) levels are not always well-controlled even by statin treatment. The glucose-lowering glucagon-like peptide-1 receptor agonists (GLP-1RAs) are reported to change the lipid profiles in T2DM patients, but their effects have been unclear. OBJECTIVE: We examined whether GLP-1RAs affect serum cholesterol levels in T2DM patients with/without statin treatment...
November 21, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29210642/antidiabetics-structural-diversity-of-molecules-with-a-common-aim
#7
Jelena B Popovic-Dordevic, Ivana I Jevtic, Tatjana P Stanojkovic
BACKGROUND: Diabetes mellitus type 2 (DMT2) is an endocrine disease of global proportions which is currently affecting 1 in 12 adults in the world, with still increasing prevalence. World Health Organization (WHO) declared this worldwide health problem, as an epidemic disease, to be the only non-infectious disease with such categorization. People with DMT2 are at increased risk of various complications and have shorter life expectancy. The main classes of oral antidiabetic drugs accessible today for DMT2 vary in their chemical composition, modes of action, safety profiles and tolerability...
December 5, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29209277/exenatide-improves-bone-quality-in-a-murine-model-of-genetically-inherited-type-2-diabetes-mellitus
#8
Marie Pereira, Stephanie Gohin, Jean-Paul Roux, Amy Fisher, Mark E Cleasby, Guillaume Mabilleau, Chantal Chenu
Type 2 diabetes mellitus (T2DM) is associated with skeletal complications, including an increased risk of fractures. Reduced blood supply and bone strength may contribute to this skeletal fragility. We hypothesized that long-term administration of Exenatide, a glucagon-like peptide-1 receptor agonist, would improve bone architecture and strength of T2DM mice by increasing blood flow to bone, thereby stimulating bone formation. In this study, we used a model of obesity and severe T2DM, the leptin receptor-deficient db/db mouse to assess alterations in bone quality and hindlimb blood flow and to examine the beneficial effects of 4 weeks administration of Exenatide...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29206860/the-acute-glucose-lowering-effect-of-specific-gpr120-activation-in-mice-is-mainly-driven-by-glucagon-like-peptide-1
#9
Linda Sundström, Susanna Myhre, Monika Sundqvist, Andrea Ahnmark, William McCoull, Piotr Raubo, Sam D Groombridge, Magnus Polla, Ann-Christin Nyström, Lisbeth Kristensson, Mats Någård, Maria Sörhede Winzell
The mechanism behind the glucose lowering effect occurring after specific activation of GPR120 is not completely understood. In this study, a potent and selective GPR120 agonist was developed and its pharmacological properties were compared with the previously described GPR120 agonist Metabolex-36. Effects of both compounds on signaling pathways and GLP-1 secretion were investigated in vitro. The acute glucose lowering effect was studied in lean wild-type and GPR120 null mice following oral or intravenous glucose tolerance tests...
2017: PloS One
https://www.readbyqxmd.com/read/29206832/the-effects-of-dipeptidyl-peptidase-4-inhibitors-on-bone-fracture-among-patients-with-type-2-diabetes-mellitus-a-network-meta-analysis-of-randomized-controlled-trials
#10
Jun Yang, Chao Huang, Shanshan Wu, Yang Xu, Ting Cai, Sanbao Chai, Zhirong Yang, Feng Sun, Siyan Zhan
AIM: The association between dipeptidyl peptidase-4 inhibitors (DPP-4is), a class of anti-diabetes, and bone fracture in patients with type 2 diabetes mellitus (T2DM) is unknown. This meta-analysis aimed to systematically evaluate the effects of DPP-4is on bone fracture in T2DM patients. METHODS: We searched the Cochrane Library, Embase, Medline and ClinicalTrials.gov from inception through April 28th, 2016 to identify randomized controlled trials (RCTs) that compared DPP-4is with placebo or other anti-diabetes in T2DM patients...
2017: PloS One
https://www.readbyqxmd.com/read/29205856/use-and-effectiveness-of-a-fixed-ratio-combination-of-insulin-degludec-liraglutide-ideglira-in-a-real-world-population-with-type-2-diabetes-results-from-a-european-multicentre-retrospective-chart-review-study
#11
Hermione Price, Matthias Blüher, Rudolf Prager, Tra-Mi Phan, Brian Larsen Thorsted, Bernd Schultes
AIMS: EXTRA aimed to describe real-world use and effectiveness of IDegLira, a fixed-ratio combination of the basal insulin degludec, and the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide. MATERIALS AND METHODS: This European, multicentre, retrospective chart review comprised adults (n=611) with type 2 diabetes, who started IDegLira ≥6 months before data collection. Clinical characteristics were assessed at baseline (defined as the most recent recording during the 6 months before the first IDegLira prescription) and 3, 6, 9 and 12 months (± 45 days for each time point) after commencing IDegLira, where data available...
December 5, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29205117/characterization-of-optimized-functional-complementary-dual-insulinotorpic-peptide-rolgg
#12
Yaofang Zhang, Li Du, Yanling Xu, Lin Tian, Peipei Tu, Minggang Li
BACKGROUND: Glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) play a similar but complementary role in the regulation of glucose levels in islet β-cells. This study was aimed to develop a fusion peptide, which combines 4 tandem repeated GLP-1 and 4 tandem repeated GIP (4rolGG), and to investigate its therapeutic effect on type 2 diabetes using a diabetic mice model. METHOD: A 4rolGG expression plasmid was constructed and expressed in BL21 (DE3)...
December 3, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/29203510/mechanisms-to-elevate-endogenous-glucagon-like-peptide-1-glp-1-beyond-injectable-glp-1-analogues-and-metabolic-surgery
#13
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/29202475/discovery-characterization-and-clinical-development-of-the-glucagon-like-peptides
#14
Daniel J Drucker, Joel F Habener, Jens Juul Holst
The discovery, characterization, and clinical development of glucagon-like-peptide-1 (GLP-1) spans more than 30 years and includes contributions from multiple investigators, science recognized by the 2017 Harrington Award Prize for Innovation in Medicine. Herein, we provide perspectives on the historical events and key experimental findings establishing the biology of GLP-1 as an insulin-stimulating glucoregulatory hormone. Important attributes of GLP-1 action and enteroendocrine science are reviewed, with emphasis on mechanistic advances and clinical proof-of-concept studies...
December 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29201871/calcitonin-gene-related-peptide-neuroendocrine-communication-between-the-pancreas-gut-and-brain-in-regulation-of-blood-glucose
#15
Sayali A Pendharkar, Monika Walia, Marie Drury, Maxim S Petrov
Background: Calcitonin gene-related peptide (CGRP), a ubiquitous neuropeptide, plays a diverse and intricate role in chronic low-grade inflammation, including conditions such as obesity, type 2 diabetes, and diabetes of the exocrine pancreas. Diabetes of exocrine pancreas is characterised by chronic hyperglycemia and is associated with persistent low-grade inflammation and altered secretion of certain pancreatic and gut hormones. While CGRP may regulate glucose homeostasis and the secretion of pancreatic and gut hormones, its role in chronic hyperglycemia after acute pancreatitis (CHAP) is not known...
November 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29201240/glucagon-like-peptide-1-potentiates-glucose-stimulated-insulin-secretion-via-the-transient-receptor-potential-melastatin-2-channel
#16
Bo Pang, Sungjoon Kim, Daiqing Li, Zejun Ma, Bei Sun, Xiaona Zhang, Zhongming Wu, Liming Chen
The transient receptor potential melastatin 2 (TRPM2) channel, a Ca2+ permeable channel activated by cAMP, is expressed on pancreatic β-cells and is responsible for the regulation of insulin secretion. It is known that glucose-stimulated insulin secretion (GSIS) can be potentiated by glucagon like peptide-1 (GLP-1), and that the changes in the extracellular glucose concentration alter the levels of intracellular adenosine ATP and cAMP. The present study hypothesized that TRPM2 mediates the modulatory effect of GLP-1 on insulin secretion...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29200876/effects-of-insulin-analogs-and-glucagon-like-peptide-1-receptor-agonists-on-proliferation-and-cellular-energy-metabolism-in-papillary-thyroid-cancer
#17
Liang He, Siliang Zhang, Xiaowen Zhang, Rui Liu, Haixia Guan, Hao Zhang
Purpose: This study was aimed to investigate the expressions of the insulin receptor (IR), insulin-like growth factor receptor (IGF-1R), and glucagon-like peptide-1 receptor (GLP-1R) in normal thyroid tissue, papillary thyroid cancer (PTC) tissues, and PTC cells, and to examine the possible role of insulin analogs and GLP-1R agonists in cell proliferation and energy metabolism in PTC cells. Methods: The expressions of IR, IGF-1R, and GLP-1R in PTC tissues and PTC cell lines were detected by immunohistochemistry and western blotting, respectively...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29200726/influence-of-flavonoids-on-mechanism-of-modulation-of-insulin-secretion
#18
Juliana Mikaelly Dias Soares, Ana Ediléia Barbosa Pereira Leal, Juliane Cabral Silva, Jackson R G S Almeida, Helinando Pequeno de Oliveira
Background: The development of alternatives for insulin secretion control in vivo or in vitro represents an important aspect to be investigated. In this direction, natural products have been progressively explored with this aim. In particular, flavonoids are potential candidates to act as insulin secretagogue. Objective: To study the influence of flavonoid on overall modulation mechanisms of insulin secretion. Methods: The research was conducted in the following databases and platforms: PubMed, Scopus, ISI Web of Knowledge, SciELO, LILACS, and ScienceDirect, and the MeSH terms used for the search were flavonoids, flavones, islets of Langerhans, and insulin-secreting cells...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29199179/on-the-relationship-between-glucose-absorption-and-glucose-stimulated-secretion-of-glp-1-neurotensin-and-pyy-from-different-intestinal-segments-in-the-rat
#19
Rune E Kuhre, Charlotte B Christiansen, Monika Y Saltiel, Nicolai J Wewer Albrechtsen, Jens J Holst
Ingested glucose powerfully stimulates the secretion of appetite- and metabolism-regulating peptide hormones from the gut - including glucagon-like peptide-1 (GLP-1), neurotensin (NT), and polypeptide YY (PYY). However, the regional origin of these secretions after glucose stimulation is not well characterized, and it remains uncertain how their secretion is related to glucose absorption. We isolated and perfused either the upper (USI) or the lower (LSI) small intestine or the colon from rats and investigated concomitant glucose absorption and secretory profiles of GLP-1, NT, and PYY In the USI and LSI luminal glucose (20%, w/v) increased GLP-1 and NT secretion five to eightfold compared to basal secretion...
December 2017: Physiological Reports
https://www.readbyqxmd.com/read/29196084/characteristics-associated-with-the-choice-of-first-injectable-therapy-among-us-patients-with-type-2-diabetes
#20
Maria Yu, Reema Mody, Laura Fernández Landó, Amy Shui, Lee Kallenbach, Lukas Slipski, Carolina Piras de Oliveira
PURPOSE: The objective of this retrospective observational study was to describe and identify clinical and demographic characteristics associated with the choice of first injectable therapy (glucagon-like peptide-1 receptor agonist [GLP-1-RA] or basal insulin) among patients with type 2 diabetes mellitus (T2DM). METHODS: This analysis included adults naive to injectable therapy with T2DM who initiated a GLP-1-RA or basal insulin (index date) between November 2014 and February 2016 using data from the Practice Fusion Electronic Health Record database...
November 28, 2017: Clinical Therapeutics
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