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GLP-1 Analogues

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https://www.readbyqxmd.com/read/28808865/glucagon-like-peptides-1-and-2-are-involved-in-satiety-modulation-after-modified-biliopancreatic-diversion-results-of-a-pilot-study
#1
Everton Cazzo, José Carlos Pareja, Elinton Adami Chaim, Cláudio Saddy Rodrigues Coy, Daniéla Oliveira Magro
BACKGROUND: This paper aimed to evaluate the influence of modified biliopancreatic diversion (BPD) on the levels of GLP-1 and GLP-2 and correlate them with satiety regulation. METHODS: This is a pilot prospective cohort study that evaluated six mildly obese individuals with type 2 diabetes mellitus, which underwent modified BPD and were followed-up for 12 months. Levels of GLP-1 and GLP-2 after a standard meal tolerance test were determined and correlated with satiety scores obtained by means of a visual analogue scale (VAS)...
August 14, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28772236/a-novel-glucagon-like-peptide-1-glucagon-receptor-dual-agonist-exhibits-weight-lowering-and-diabetes-protective-effects
#2
Jie Zhou, Xingguang Cai, Xun Huang, Yuxuan Dai, Lidan Sun, Bo Zhang, Bo Yang, Haiyan Lin, Wenlong Huang, Hai Qian
Glucagon has plenty of effects via a specific glucagon receptor(GCGR) like elevating the blood glucose, improving fatty acids metabolism, energy expenditure and increasing lipolysis in adipose tissue. The most important role of glucagon is to regulate the blood glucose, but the emergent possibilities of hyperglycaemia is exist. Glucagon could also slightly activate glucagon-like peptide-1 receptor(GLP-1R), which lead to blood glucose lowering effect. This study aims to erase the likelihood of hyperglycaemia and to remain the inherent catabolic effects through improving GLP-1R activation and deteriorating GCGR activation so as to lower the bodyweight and show diabetes-protective effects...
July 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28771355/peptide-half-life-extension-divalent-small-molecule-albumin-interactions-direct-the-systemic-properties-of-glucagon-like-peptide-1-glp-1-analogues
#3
Esben M Bech, Manuel C Maldonado, Pernille Wismann, Kasper K Sørensen, Søren Blok van Witteloostuijn, Mikkel B Thygesen, Niels Vrang, Jacob Jelsing, Søren L Pedersen, Knud J Jensen
Noncovalent binding of biopharmaceuticals to human serum albumin protects against enzymatic degradation and renal clearance. Herein, we investigated the effect of mono- or divalent small-molecule albumin binders for half-life extension of peptides. For proof-of-principle, the clinically relevant glucagon-like peptide 1 (GLP-1) was functionalized with diflunisal, indomethacin, or both. In vitro, all GLP-1 analogues had subnanomolar GLP-1 receptor potency. Surface plasmon resonance revealed that both small molecules were able to confer albumin affinity to GLP-1 and indicated that affinity is increased for divalent analogues...
August 16, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28763620/acute-effects-of-exercise-intensity-on-subsequent-substrate-utilisation-appetite-and-energy-balance-in-men-and-women
#4
Ghalia Shamlan, Paul Bech, M Denise Robertson, Adam L Collins
Exercise is capable of influencing the regulation of energy balance by acutely modulating appetite and energy intake coupled to effects on substrate utilization. Yet, few studies have examined acute effects of exercise intensity on aspects of both energy intake and energy metabolism, independently of energy cost of exercise. Furthermore, little is known as to the gender differences of these effect. One hour after a standardised breakfast, 40 (19 female), healthy participants (BMI 23.6±3.6 kg.m-2, VO2peak 34...
August 1, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28741970/efficacy-and-safety-of-once-weekly-semaglutide-for-the-treatment-of-type-2-diabetes
#5
Xueying Tan, Xiaojing Cao, Minzhi Zhou, Ping Zou, Jingbo Hu
Type 2 diabetes is a chronic metabolic disease characterized by persistent hyperglycemia resulting from progressive deficient of insulin in patients with a background of insulin resistance. Current treatment algorithms recommended by American Diabetes Association/The European Association for the Study of Diabetes promote a patient-centered approach that takes into account a comprehensive consideration of pharmacological properties of drugs, including glucose-lowering action, effects on body weight, correction on multiple pathophysiologic defects, tolerability, and long-term safety...
July 25, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28734203/exenatide-mitigated-diet-induced-vascular-aging-and-atherosclerotic-plaque-growth-in-apoe-deficient-mice-under-chronic-stress
#6
Guang Yang, Yanna Lei, Aiko Inoue, Limei Piao, Lina Hu, Haiying Jiang, Takeshi Sasaki, Hongxian Wu, Wenhu Xu, Chenglin Yu, Guangxian Zhao, Shinyu Ogasawara, Kenji Okumura, Masafumi Kuzuya, Xian-Wu Cheng
BACKGROUND AND AIMS: Exposure to psychosocial stress is a risk factor for cardiovascular disorders. Because the glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonist prevents cardiovascular injury, we investigated the beneficial effects and mechanism of the GLP-1 analogue exenatide on stress-related vascular senescence and atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice fed a high-fat (HF) diet. METHODS: ApoE(-/-) mice fed the HF diet were assigned to non-stressed and immobilized-stress groups for 12 weeks...
July 13, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28730832/liraglutide-preserves-intracellular-calcium-handling-in-isolated-murine-myocytes-exposed-to-oxidative-stress
#7
S Palee, S C Chattipakorn, N Chattipakorn
In ischemic/reperfusion (I/R) injured hearts, severe oxidative stress occurs and is associated with intracellular calcium (Ca(2+)) overload. Glucagon-Like Peptide 1 (GLP-1) analogues have been shown to exert cardioprotection in I/R heart. However, there is little information regarding the effects of GLP-1 analogue on the intracellular Ca(2+) regulation in the presence of oxidative stress. Therefore, we investigated the effects of GLP-1 analogue, (liraglutide, 10 microM) applied before or after hydrogen peroxide (H(2)O(2), 50 microM) treatment on intracellular Ca(2+) regulation in isolated cardiomyocytes...
July 18, 2017: Physiological Research
https://www.readbyqxmd.com/read/28730824/glucagon-like-peptide-1-analogues-exenatide-and-liraglutide-exert-inhibitory-effect-on-the-early-phase-of-liver-regeneration-after-partial-hepatectomy-in-rats
#8
J Fontana, O Kučera, V Mezera, M Anděl, Z Červinková
Glucagon-like peptide-1 (GLP-1) is an incretin known for proliferative and antiapoptotic effects on various tissues. Exenatide and Liraglutide are GLP-1 analogues used in clinical practice as antidiabetic drugs. Since GLP-1 and its analogues exert significant effect on liver metabolism and since changes in intermediary metabolism play an important role in the process of liver regeneration, we decided to determine the effect of Exenatide and Liraglutide on the early phase of liver regeneration and selected metabolic parameters in a model of 2/3 partial hepatectomy (PHx) in rats...
July 18, 2017: Physiological Research
https://www.readbyqxmd.com/read/28730728/beneficial-long-term-antidiabetic-actions-of-n-and-c-terminally-modified-analogues-of-apelin-13-in-diet-induced-obese-diabetic-mice
#9
V Parthsarathy, C Hogg, P R Flatt, F P M O'Harte
AIMS: This study investigated the chronic effects of twice daily administration of stable apelin analogues, apelin-13 amide and (pGlu)apelin-13 amide, on metabolic parameters in glucose intolerant and insulin resistant diet-induced obese (DIO) mice fed a high-fat diet for 150 days. STUDY DESIGN & METHODS: Groups of mice received twice daily (09:00 and 17:00 h) injections of saline vehicle, apelin-13 amide, (pGlu)apelin-13 amide or exendin-4(1-39) for 28 days (all at 25 nmol/kg)...
July 20, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28713911/glucagon-like-peptide-1-analogue-liraglutide-ameliorates-atherogenesis-via-inhibiting-advanced-glycation-end-product-induced-receptor-for-advanced-glycosylation-end-product-expression-in-apolipoprotein-e-deficient-mice
#10
Peicheng Li, Zhaosheng Tang, Lin Wang, Bo Feng
Glucagon-like peptide-1 (GLP-1) can protect arteriosclerotic lesions in apolipoprotein-E deficient (ApoE-/-) mice. Advanced glycation end products (AGEs)/receptor for advanced glycation end products (RAGE) interaction serves a key role in the development of diabetic vascular complications. The present study examined whether the GLP-1 analogue liraglutide can ameliorate atherogenesis via inhibiting AGEs-induced RAGE expression. Male ApoE-/- mice (age, 10 weeks) were divided into control, GLP-1, AGEs and AGEs+GLP-1 group...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28712893/the-glucagon-like-peptide-1-analogue-liraglutide-promotes-autophagy-through-the-modulation-of-5-amp-activated-protein-kinase-in-ins-1-%C3%AE-cells-under-high-glucose-conditions
#11
Xinyu Miao, Zhaoyan Gu, Yu Liu, Mengmeng Jin, Yanhui Lu, Yanping Gong, Lin Li, Chunlin Li
Glucagon-like peptide-1 (GLP-1) is a potent therapeutic agent for the treatment of diabetes and has been proven to protect pancreatic β-cells from glucotoxicity; however, its mechanisms of action are not entirely understood. Autophagy is a dynamic lysosomal degradation process that can protect organisms against metabolic stress. Studies have shown that autophagy plays a protective role in the survival of pancreatic β-cells under high glucose conditions. In the present study, we explored the role of autophagy in GLP-1-induced protection of pancreatic β-cells exposed to high glucose...
July 13, 2017: Peptides
https://www.readbyqxmd.com/read/28701318/%C3%A2-liraglutide-for-weight-management
#12
(no author information available yet)
Since 1950, 25 anti-obesity drugs have been withdrawn from use across the world, largely as a result of adverse effects.(1) For several years, orlistat has been the only drug licensed in the UK for weight management.(2) In January 2017, a new presentation of the glucagon-like peptide-1 (GLP-1) analogue liraglutide (▾Saxenda - Novo Nordisk) was launched in the UK as an adjunct to a reduced-calorie diet and increased physical activity for weight management in adults. Here, we review the evidence for its efficacy and safety and consider its place in managing people who are overweight or obese...
July 2017: Drug and Therapeutics Bulletin
https://www.readbyqxmd.com/read/28688914/glucagon-and-glucagon-like-peptide-1-as-novel-anti-inflammatory-and-immunomodulatory-compounds
#13
REVIEW
Daniella B R Insuela, Vinicius F Carvalho
Glucagon and glucagon-like peptide-1 (GLP-1) are polypeptide hormones that are produced by pancreatic α-cells and the intestine, respectively, whose main function is to control glucose homeostasis. The glucagon and GLP-1 levels are imbalanced in diabetes. Furthermore, type 1 diabetic patients and animals present with a diminished inflammatory response, which is related to some morbidities of diabetes, such as a higher incidence of infectious diseases, including sepsis. The focus of this review is to briefly summarize the state of the art concerning the effects of glucagon and GLP-1 on the inflammatory response...
July 6, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28677333/review-article-new-treatments-in-non-alcoholic-fatty-liver-disease
#14
REVIEW
S A Townsend, P N Newsome
BACKGROUND: Non-alcoholic fatty liver disease is the fastest growing cause of liver disease in the Western world, yet there is no approved pharmacotherapy. While lifestyle modifications remain the mainstay of treatment, only a proportion of individuals are able to make or sustain them, and so more treatment options are required. AIM: To review the potential benefit of drugs used in clinical practice, those entering phase II trials, and compounds being investigated in pre-clinical studies...
July 4, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28667587/insulin-glargine-lixisenatide-a-review-in-type-2-diabetes
#15
Lesley J Scott
Subcutaneous insulin glargine/lixisenatide (Suliqua™) is a titratable, fixed-ratio combination of a long-acting basal insulin analogue and a glucagon-like peptide-1 (GLP-1) receptor agonist for the treatment of adult patients with inadequately controlled type 2 diabetes. Once-daily insulin glargine/lixisenatide, in combination with metformin, provided effective glycaemic control and was generally well tolerated in the 30-week, multinational, phase 3 LixiLan-O and LixiLan-L trials in insulin-naive and -experienced adult patients with inadequately controlled type 2 diabetes...
August 2017: Drugs
https://www.readbyqxmd.com/read/28666800/a-novel-glp-1-gip-dual-agonist-is-more-effective-than-liraglutide-in-reducing-inflammation-and-enhancing-gdnf-release-in-the-mptp-mouse-model-of-parkinson-s-disease
#16
Ziyue Yuan, Dongfang Li, Peng Feng, Guofang Xue, Chenhui Ji, Guanglai Li, Christian Hölscher
Type 2 diabetes mellitus (T2DM) is one of the risk factors for Parkinson's disease (PD). Insulin desensitisation has been observed in the brains of patients, which may promote neurodegeneration. Incretins are a family of growth factors that can re-sensitise insulin signalling. We have previously shown that mimetics of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP) mouse model of PD...
June 27, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28664354/impact-of-medicine-withdrawal-on-reporting-of-adverse-events-involving-therapeutic-alternatives-a-study-from-the-french-spontaneous-reporting-database
#17
Cécile Pageot, Julien Bezin, Andy Smith, Mickael Arnaud, Francesco Salvo, Françoise Haramburu, Bernard Bégaud, Antoine Pariente
INTRODUCTION: The consequences of the withdrawal of marketing authorisation of drugs have mostly been studied considering drug prescription patterns for the therapeutic alternatives of the withdrawn drugs. The potential concomitant changes in the reporting of adverse reactions concerning these alternatives have been studied less often. OBJECTIVE: The objective of this study was to analyse the changes in the reporting of adverse events (AEs) for therapeutic alternatives after the withdrawal of three medicines (dextropropoxyphene, pioglitazone and tetrazepam) from the market for safety reasons...
June 29, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/28662391/gold-nanoparticles-as-an-efficient-drug-delivery-system-for-glp-1-peptides
#18
Magdalena Pérez-Ortiz, Claudio Zapata-Urzúa, Gerardo A Acosta, Alejandro Álvarez-Lueje, Fernando Albericio, Marcelo J Kogan
In this work, the potential application of gold nanoparticles for GLP-1 analogues delivery was studied. For this purpose, the original sequence of the incretin GLP-1 was slightly modified in the C-terminal region by adding a cysteine residue to facilitate conjugation to the gold surface. The interaction between peptides and gold nanoparticles and also the colloid stability of the conjugates were studied by UV-vis spectrophotometry, TEM, IR and XPS spectroscopy. Moreover, the permeability of these conjugates was assayed using a Caco-2/goblet monolayer model...
June 19, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28619366/bpi-3016-a-novel-long-acting-hglp-1-analogue-for-the-treatment-of-type-2-diabetes-mellitus
#19
Lieming Ding, Sisi Lu, Yanping Wang, Haibo Chen, Wei Long, Cunbo Ma, Erlong He, Dan Yan, Fenlai Tan
Glucagon-like peptide-1 (GLP-1) analogues have been commonly used as add-on medications for patients with Type 2 diabetes mellitus (T2DM). Currently, the development of long-acting GLP-1 analogues which allow the freedom and flexibility of once-weekly injections while maintaining their potency for a relatively long period has become the mainstream. Here, we successfully developed a long-acting human GLP-1(7-37) analogue (BPI-3016) with significantly extended half-life and increased resistance to dipeptidyl peptidase IV (DPP-IV) cleavage by structural modifications of human GLP-1...
August 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28608285/the-glp-1-analogue-lixisenatide-decreases-atherosclerosis-in-insulin-resistant-mice-by-modulating-macrophage-phenotype
#20
Ángela Vinué, Jorge Navarro, Andrea Herrero-Cervera, Marta García-Cubas, Irene Andrés-Blasco, Sergio Martínez-Hervás, José T Real, Juan F Ascaso, Herminia González-Navarro
AIMS/HYPOTHESIS: Recent clinical studies indicate that glucagon-like peptide-1 (GLP-1) analogues prevent acute cardiovascular events in type 2 diabetes mellitus but their mechanisms remain unknown. In the present study, the impact of GLP-1 analogues and their potential underlying molecular mechanisms in insulin resistance and atherosclerosis are investigated. METHODS: Atherosclerosis development was evaluated in Apoe (-/-) Irs2 (+/-) mice, a mouse model of insulin resistance, the metabolic syndrome and atherosclerosis, treated with the GLP-1 analogues lixisenatide or liraglutide...
June 12, 2017: Diabetologia
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