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GLP-1 Analogues

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https://www.readbyqxmd.com/read/28057699/glucagon-like-peptide-1-and-its-analogues-act-in-the-dorsal-raphe-and-modulate-central-serotonin-to-reduce-appetite-and-body-weight
#1
Rozita H Anderberg, Jennifer E Richard, Kim Eerola, Lorena Lopez Ferreras, Elin Banke Nordbeck, Caroline Hansson, Hans Nissbrandt, Filip Berqquist, Fiona M Gribble, Frank Reimann, Ingrid Wernstedt-Asterholm, Christophe Lamy, Karolina P Skibicka
Glucagon-like peptide-1 (GLP-1) and serotonin play critical roles in energy balance regulation. Both systems are exploited clinically as anti-obesity strategies. Surprisingly whether they interact in order to regulate energy balance is poorly understood. Here we investigated mechanisms by which GLP-1 and serotonin interact at the level of the CNS. Serotonin depletion impaired the ability of exendin-4, a clinically utilized GLP-1 analogue, to reduce body weight in rats, suggesting serotonin is a critical mediator of the energy balance impact of GLP-1R activation...
January 5, 2017: Diabetes
https://www.readbyqxmd.com/read/28049736/glp-1-analogue-induced-weight-loss-does-not-improve-obesity-induced-at-dysfunction
#2
Emilie Pastel, Laura J McCulloch, Rebecca Ward, Shivam Joshi, Kim M Gooding, Angela C Shore, Katarina Kos
Glucagon-like peptide-1 (GLP-1) analogues aid weight loss which improves obesity-associated adipose tissue (AT) dysfunction. GLP-1 treatment may however also directly influence AT which expresses GLP-1 receptors. This study aimed to assess the impact of GLP-1 analogue treatment on subcutaneous AT inflammatory and fibrotic responses, compared to weight loss by calorie reduction (control). Among the 39 participants with type 2 diabetes recruited, 30 age-matched participants were randomised to 4 months treatment with Liraglutide (n=22) or calorie restriction-based on dietetic counselling (n=8)...
January 3, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28031776/glucagon-like-peptide-1-in-the-pathophysiology-and-pharmacotherapy-of-clinical-obesity
#3
REVIEW
Ananthi Anandhakrishnan, Márta Korbonits
Though the pathophysiology of clinical obesity is undoubtedly multifaceted, several lines of clinical evidence implicate an important functional role for glucagon-like peptide 1 (GLP-1) signalling. Clinical studies assessing GLP-1 responses in normal weight and obese subjects suggest that weight gain may induce functional deficits in GLP-1 signalling that facilitates maintenance of the obesity phenotype. In addition, genetic studies implicate a possible role for altered GLP-1 signalling as a risk factor towards the development of obesity...
December 15, 2016: World Journal of Diabetes
https://www.readbyqxmd.com/read/28008585/glucagon-like-peptide-1-analogues-inhibit-proliferation-and-increase-apoptosis-of-human-prostate-cancer-cells-in-vitro
#4
X-N Li, H-M Bu, X-H Ma, Sh Lu, Sh Zhao, Y-L Cui, J Sun
Background: Research has shown that the incidence of prostate cancer is increased in patients with type 2 diabetes mellitus (T2DM) 1. Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone that enhances glucose-dependent insulin secretion and suppresses glucagon release. Method: Here, we examined the effect of exenatide and liraglutide, 2 types of GLP-1 analogues, on prostate cancer cells growth by CCK-8 assay, Hoechst33258 staining assay, and western blot analysis of apoptosis-related proteins Bax and Bcl-2...
December 22, 2016: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28007055/physiological-and-pathophysiological-aspects-of-incretin-hormones-and-glucagon
#5
Jonatan Ising Bagger
Infusion of oxyntomodulin and the separate and combined infusion of GLP-1 and glucagon inhibited food intake similarly in healthy individuals, with no superior effect of combining GLP-1 and glucagon. We confirm the inhibitory effects of oxyntomodulin and GLP-1, respectively, on GE and appetite scores observed previously, but by adding glucagon to the infusion of GLP-1 we found no additive effects. Unexpectedly, glucagon alone had no effect on GE and appetite scores, but inhibited food intake to the same extent as oxyntomodulin, GLP-1 and GLP-1 + glucagon...
January 2017: Danish Medical Journal
https://www.readbyqxmd.com/read/28005376/neoglycolipids-for-prolonging-the-effects-of-peptides-self-assembling-glucagon-like-peptide-1-analogues-with-albumin-binding-properties-and-potent-in-vivo-efficacy
#6
Søren B van Witteloostuijn, Karin Mannerstedt, Pernille Wismann, Esben M Bech, Mikkel B Thygesen, Niels Vrang, Jacob Jelsing, Knud J Jensen, Søren L Pedersen
Novel principles for optimizing the properties of peptide-based drugs are needed in order to leverage their full pharmacological potential. We present the design, synthesis, and evaluation of a library of neoglycolipidated glucagon-like peptide 1 (GLP-1) analogues, which are valuable drug candidates for treatment of type 2 diabetes and obesity. Neoglycolipidation of GLP-1 balanced the lipophilicity, directed formation of soluble oligomers, and mediated albumin binding. Moreover, neoglycolipidation did not compromise bioactivity, as in vitro potency of neoglycolipidated GLP-1 analogues was maintained or even improved compared to native GLP-1...
January 3, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27998088/a-ph-induced-switch-in-human-glucagon-like-peptide-1-aggregation-kinetics
#7
Karolina L Zapadka, Frederik J Becher, Shahid Uddin, Paul G Varley, Steve Bishop, A L Gomes Dos Santos, Sophie E Jackson
Aggregation and amyloid fibril formation of peptides and proteins is a widespread phenomenon. It has serious implications in a range of areas from biotechnological and pharmaceutical applications to medical disorders. The aim of this study was to develop a better understanding of the mechanism of aggregation and amyloid fibrillation of an important pharmaceutical, human glucagon-like peptide-1 (GLP-1). GLP-1 is a 31-residue hormone peptide that plays an important role regulating blood glucose levels, analogues of which are used for treatment of type 2 diabetes...
December 21, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27993221/exendin-4-a-glucagon-like-peptide-1-analogue-accelerates-diabetic-wound-healing
#8
Jun-Neng Roan, Han-Ni Cheng, Chao-Chung Young, Chi-Ju Lee, Ming-Long Yeh, Chwan-Yau Luo, Yau-Sheng Tsai, Chen-Fuh Lam
BACKGROUND: Diabetes disregulates inflammatory responses and impairs vascular function in wounds. Glucagon-like peptide-1 receptor (Glp-1R) agonists are hypoglycemic agents with pleiotropic vascular protective and anti-inflammatory effects. The therapeutic potential of a Glp-1 analogue in a diabetic rat model of excisional wound injury was investigated. MATERIALS AND METHODS: Excisional wounds were created on the dorsum of streptozotocin-induced diabetic rats, which received placebo or Glp-1 analogue exendin-4 (Ex4; 0...
February 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/27992511/liraglutide-reduces-both-atherosclerosis-and-kidney-inflammation-in-moderately-uremic-ldlr-mice
#9
Line S Bisgaard, Markus H Bosteen, Lisbeth N Fink, Charlotte M Sørensen, Alexander Rosendahl, Christina K Mogensen, Salka E Rasmussen, Bidda Rolin, Lars B Nielsen, Tanja X Pedersen
Chronic kidney disease (CKD) leads to uremia. CKD is characterized by a gradual increase in kidney fibrosis and loss of kidney function, which is associated with a progressive increase in risk of atherosclerosis and cardiovascular death. To prevent progression of both kidney fibrosis and atherosclerosis in uremic settings, insight into new treatment options with effects on both parameters is warranted. The GLP-1 analogue liraglutide improves glucose homeostasis, and is approved for treatment of type 2 diabetes...
2016: PloS One
https://www.readbyqxmd.com/read/27986341/incretin-related-drugs-and-cardiovascular-events-a-comparison-of-glp-1-analogue-and-dpp-4-inhibitor
#10
EDITORIAL
Yukihito Higashi
No abstract text is available yet for this article.
December 13, 2016: Journal of Cardiology
https://www.readbyqxmd.com/read/27941938/effects-of-exendin-4-on-human-adipose-tissue-inflammation-and-ecm-remodelling
#11
E Pastel, S Joshi, B Knight, N Liversedge, R Ward, K Kos
BACKGROUND/OBJECTIVES: Subjects with type-2 diabetes are typically obese with dysfunctional adipose tissue (AT). Glucagon-like peptide-1 (GLP-1) analogues are routinely used to improve glycaemia. Although, they also aid weight loss that improves AT function, their direct effect on AT function is unclear. To explore GLP-1 analogues' influence on human AT's cytokine and extracellular matrix (ECM) regulation, we therefore obtained and treated omental (OMAT) and subcutaneous (SCAT) AT samples with Exendin-4, an agonist of the GLP-1 receptor (GLP-1R)...
December 12, 2016: Nutrition & Diabetes
https://www.readbyqxmd.com/read/27929679/glp-1-analogues-for-the-treatment-of-type-2-diabetes-in-latinos-hispanics
#12
A Enrique Caballero
No abstract text is available yet for this article.
December 2016: Endocrine Practice
https://www.readbyqxmd.com/read/27912784/liraglutide-improves-metabolic-parameters-and-carotid-intima-media-thickness-in-diabetic-patients-with-the-metabolic-syndrome-an-18-month-prospective-study
#13
Manfredi Rizzo, Ali A Rizvi, Angelo Maria Patti, Dragana Nikolic, Rosaria Vincenza Giglio, Giuseppa Castellino, Giovanni Li Volti, Massimiliano Caprio, Giuseppe Montalto, Vincenzo Provenzano, Stefano Genovese, Antonio Ceriello
BACKGROUND: Liraglutide, a GLP-1 analogue, exerts several beneficial non-glycemic effects in patients with type-2 diabetes (T2DM), such as those on body weight, blood pressure, plasma lipids and inflammation markers. However, the effects of liraglutide on cardiovascular (CV) risk markers in subjects with the metabolic syndrome (MetS) are still largely unknown. We herein explored its effects on various cardio-metabolic risk markers of the MetS in subjects with T2DM. METHODS: We performed an 18-month prospective, real-world study...
December 3, 2016: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/27878229/glucagon-like-peptide-1-improves-insulin-resistance-in-vitro-through-anti-inflammation-of-macrophages
#14
C Guo, T Huang, A Chen, X Chen, L Wang, F Shen, X Gu
Glucagon-like peptide 1 (GLP-1), a kind of gut hormone, is used in the treatment of type 2 diabetes (T2D). Emerging evidence indicates that GLP-1 has anti-inflammatory activity. Chronic inflammation in the adipose tissue of obese individuals is a cause of insulin resistance and T2D. We hypothesized that GLP-1 analogue therapy in patients with T2D could suppress the inflammatory response of macrophages, and therefore inhibit insulin resistance. Our results showed that GLP-1 agonist (exendin-4) not only attenuated macrophage infiltration, but also inhibited the macrophage secretion of inflammatory cytokines including TNF-β, IL-6, and IL-1β...
November 21, 2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/27878211/liraglutide-enhances-the-efficacy-of-human-mesenchymal-stem-cells-in-preserving-islet-%C3%AE-cell-function-in-severe-non-obese-diabetic-mice
#15
Li-Rong Li, Xiao-Lei Jia, Hui Hui, Jie Zhang, Ying Liu, Wei-Juan Cui, Qian-Yue Xu, Da-Long Zhu
Glucagon-like peptide 1 (GLP-1) can promote islet β-cell replication and function, and mesenchymal stem cells (MSCs) can inhibit T cell autoimmunity. This study aimed at testing the dynamic distribution of infused human MSCs and therapeutic effect of combined MSCs and Liraglutide, a long-acting GLP-1 analogue, on preserving β-cell function in severe non-obese diabetic (NOD) mice. We found that infused MSCs accumulated in the pancreas at 4 weeks post infusion, which was not affected by Liraglutide treatment...
November 17, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27865185/a-new-era-in-the-management-of-type-2-diabetes-is-cardioprotection-at-long-last-a-reality
#16
EDITORIAL
Xavier Rossello, Derek M Yellon
The EMPA-REG OUTCOME and the LEADER trials have revealed a new era in the management of type 2 diabetes. The SGLT2 inhibitor empagliflozin demonstrated a lower rate of the primary composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke compared to placebo. Liraglutide, a GLP-1 analogue, succeeded to demonstrate reduction on a composite outcome including first occurrence of cardiovascular death, nonfatal myocardial infarction or non-fatal stroke. These two medications act through different mechanisms and has consequently shown different patterns of cardiovascular benefit...
February 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/27823935/glucose-enhances-rat-islet-function-via-stimulating-cart-expression
#17
Wan Xu, Yuqing Zhang, Mengyao Bai, Feiye Zhou, Ruyuan Deng, Xueying Ji, Juan Zhang, Yun Liu, Libin Zhou, Xiao Wang
Cocaine- and amphetamine-regulated transcript (CART) is an anorexigenic peptide widely expressed in the central and peripheral nervous systems, as well as in endocrine cells. CART is markedly upregulated in the β-cells of several rodent models of type-2 diabetes. The stimulatory effect of exogenous CART peptide on insulin secretion is cAMP dependent. Glucose is the most important regulator of islet function. However, the role of CART in glucose-potentiated insulin secretion remains unclear. Here, our results showed that glucose time- and dose-dependently elicited CART mRNA expression in rat islets...
December 2, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27813409/%C3%AE-arrestin-biased-agonists-of-the-glp-1-receptor-from-%C3%AE-amino-acid-residue-incorporation-into-glp-1-analogues
#18
Marlies V Hager, Lisa M Johnson, Denise Wootten, Patrick M Sexton, Samuel H Gellman
Activation of a G protein-coupled receptor (GPCR) causes recruitment of multiple intracellular proteins, each of which can activate distinct signaling pathways. This complexity has engendered interest in agonists that preferentially stimulate subsets among the natural signaling pathways ("biased agonists"). We have examined analogues of glucagon-like peptide-1 (GLP-1) containing β-amino acid residues in place of native α residues at selected sites and found that some analogues differ from GLP-1 in terms of their relative abilities to promote G protein activation (as monitored via cAMP production) versus β-arrestin recruitment (as monitored via BRET assays)...
November 16, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27811949/small-intestinal-protein-infusion-in-humans-evidence-for-a-location-specific-gradient-in-intestinal-feedback-on-food-intake-and-gi-peptide-release
#19
M van Avesaat, D Ripken, H F J Hendriks, A A M Masclee, F J Troost
BACKGROUND: Protein infusion in the small intestine results in intestinal brake activation: a negative feedback mechanism that may be mediated by the release of GI peptides resulting in a reduction in food intake. It has been proposed that duodenum, jejunum and ileum may respond differently to infused proteins. OBJECTIVE: To investigate differences in ad libitum food intake, feelings of hunger and satiety and the systemic levels of cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), glucose and insulin after intraduodenal, intrajejunal and intraileal protein infusion...
November 4, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/27797785/glucagon-like-peptide-1-analogues-and-risk-of-breast-cancer-in-women-with-type-2-diabetes-population-based-cohort-study-using-the-uk-clinical-practice-research-datalink
#20
Blánaid M Hicks, Hui Yin, Oriana H Y Yu, Michael N Pollak, Robert W Platt, Laurent Azoulay
OBJECTIVE:  To determine whether the use of glucagon-like peptide-1 (GLP-1) analogues, compared with the use of dipeptidylpeptidase-4 (DPP-4) inhibitors, is associated with an increased risk of incident breast cancer in patients with type 2 diabetes. DESIGN:  Population based cohort study. SETTING:  Clinical Practice Research Datalink, UK. PARTICIPANTS:  44 984 women aged at least 40 years, who were newly treated with glucose lowering drugs between 1 January 2007 and 31 March 2015, with follow-up until 31 March 2016...
October 20, 2016: BMJ: British Medical Journal
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