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GLP-1 Analogues

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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
#1
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
#2
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
#3
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
#4
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...
November 12, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27823935/glucose-enhances-rat-islet-function-via-stimulating-cart-expression
#5
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
#6
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 4, 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
#7
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
#8
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
https://www.readbyqxmd.com/read/27777063/liraglutide-restores-angiogenesis-in-palmitate-impaired-human-endothelial-cells-through-pi3k-akt-foxo1-gtpch1-pathway
#9
Jing Ke, Rui Wei, Fei Yu, Jingjing Zhang, Tianpei Hong
Glucagon-like peptide-1 (GLP-1) and its analogues have a beneficial role in cardiovascular system. Here, we aimed to investigate whether liraglutide, a GLP-1 analogue, modulated angiogenesis impaired by palmitic acid (PA) in cultured human umbilical vein endothelial cells (HUVECs). Cells were incubated with liraglutide (3-100 nmol/L) in the presence of PA (0.5mmol/L), and endothelial tube formation was observed and quantified. The protein levels of signaling molecules were analyzed and the specific inhibitors were used to identify the signaling pathways through which liraglutide affected angiogenesis...
December 2016: Peptides
https://www.readbyqxmd.com/read/27776993/lixisenatide-attenuates-the-detrimental-effects-of-amyloid-%C3%AE-protein-on-spatial-working-memory-and-hippocampal-neurons-in-rats
#10
Hong-Yan Cai, Zhao-Jun Wang, Christian Hölscher, Li Yuan, Jun Zhang, Peng Sun, Jing Li, Wei Yang, Mei-Na Wu, Jin-Shun Qi
Type 2 diabetes mellitus(T2DM) is a risk factor of Alzheimer's disease (AD), which is most likely linked to impairments of insulin signaling in the brain. Hence, drugs enhancing insulin signaling may have therapeutic potential for AD. Lixisenatide, a novel long-lasting glucagon-like peptide 1 (GLP-1) analogue, facilitates insulin signaling and has neuroprotective properties. We previously reported the protective effects of lixisenatide on memory formation and synaptic plasticity. Here, we describe additional key neuroprotective properties of lixisenatide and its possible molecular and cellular mechanisms against AD-related impairments in rats...
October 21, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27771154/incretin-treatment-and-atherosclerotic-plaque-stability-role-of-adiponectin-appl1-signaling-pathway
#11
Michelangela Barbieri, Raffaele Marfella, Antonietta Esposito, Maria Rosaria Rizzo, Edith Angellotti, Ciro Mauro, Mario Siniscalchi, Fabio Chirico, Pasquale Caiazzo, Fulvio Furbatto, Alessandro Bellis, Nunzia D'Onofrio, Milena Vitiello, Franca Ferraraccio, Giuseppe Paolisso, Maria Luisa Balestrieri
AIMS: Glucagon like peptide 1 (GLP-1) analogues and dipeptidyl peptidase IV (DPP-4) inhibitors reduce atherosclerosis progression in type 2 diabetes mellitus (T2DM) patients and are associated with morphological and compositional characteristics of stable plaque phenotype. GLP-1 promotes the secretion of adiponectin which exerts anti-inflammatory effects through the adaptor protein PH domain and leucine zipper containing 1 (APPL1). The potential role of APPL1 expression in the evolution of atherosclerotic plaque in TDM2 patients has not previously evaluated...
October 5, 2016: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/27766537/a-novel-bioresorbable-device-as-a-controlled-release-system-for-protecting-cells-from-oxidative-stress-from-alzheimer-s-disease
#12
Geisa Nogueira Salles, Fernanda Aparecida Dos Santos Pereira, Cristina Pacheco-Soares, Fernanda Roberta Marciano, Christian Hölscher, Thomas J Webster, Anderson Oliveira Lobo
Bioresorbable electrospun fibres have highly functional features that can preserve drug efficacy, avoiding premature degradation, and control drug release rates over long periods. In parallel, it is known that Alzheimer's disease (AD) has been linked to impaired insulin signalling in the brain. Glucagon-like peptide 1 (GLP-1) analogues have beneficial effects on insulin release and possess exceptional neuroprotective properties. Herein, we describe for the first time the incorporation of a GLP-1 analogue, liraglutide, into electrospun poly (lactic acid) (PLA) fibres with in situ gelatin capsules, in order to provide the controlled release of liraglutide, improving neuroprotective properties...
October 20, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27765008/sglt2-inhibitors-in-diabetes-mellitus-treatment
#13
Juan Rosas-Guzmán, Juan Rosas-Saucedo, Alma R J Romero-García
Type 2 Diabetes Mellitus (T2DM) is a chronic illness with high prevalence in Mexico, Latin-America, and the world and is associated to high morbidity, disability, and mortality rate, especially in developing countries. T2DM physiopathology is very complex; insulin resistance in the muscle, liver, and adipose tissue, a reduction in the production of incretins (mainly GLP-1) in the intestine, increased glucagon synthesis, an insufficient response of insulin generation, and increased glucose reabsorption in the kidney lead all together to an hyperglycemic state, which has been closely associated with the development of micro and macrovascular complications...
August 29, 2016: Reviews on Recent Clinical Trials
https://www.readbyqxmd.com/read/27744013/use-of-healthcare-resources-and-costs-associated-to-the-start-of-treatment-with-injectable-drugs-in-patients-with-type-2-diabetes-mellitus
#14
Antoni Sicras-Mainar, Ruth Navarro-Artieda, Raúl Morano, Lucía Ruíz
OBJECTIVES: The main objective was to assess resource use and costs of starting treatment with insulin or injectable GLP-1 receptor analogues (GLP-1 RAs) in a Spanish population of patients with type 2 diabetes mellitus. Treatment adherence and persistence were also determined for both treatment groups. PATIENTS AND METHODS: A retrospective, non-interventional, observational study was conducted. Patients aged ≥20 years who started treatment with insulin or GLP-1 RAs in the 2010-2012 period were recruited...
December 2016: Endocrinología y Nutrición: órgano de la Sociedad Española de Endocrinología y Nutrición
https://www.readbyqxmd.com/read/27698937/activation-of-glp-1-receptor-enhances-neuronal-base-excision-repair-via-pi3k-akt-induced-expression-of-apurinic-apyrimidinic-endonuclease-1
#15
Jenq-Lin Yang, Wei-Yu Chen, Yin-Ping Chen, Chao-Ying Kuo, Shang-Der Chen
Glucagon-like peptide-1 (GLP-1) is an intestinal-secreted incretin that increases cellular glucose up-take to decrease blood sugar. Recent studies, however, suggest that the function of GLP-1 is not only to decrease blood sugar, but also acts as a neurotrophic factor that plays a role in neuronal survival, neurite outgrowth, and protects synaptic plasticity and memory formation from effects of β-amyloid. Oxidative DNA damage occurs during normal neuron-activity and in many neurological diseases. Our study describes how GLP-1 affected the ability of neurons to ameliorate oxidative DNA damage...
2016: Theranostics
https://www.readbyqxmd.com/read/27696231/combination-therapy-with-glp-1-analogues-and-sglt-2-inhibitors-in-the-management-of-diabesity-the-real-world-experience
#16
Herpreet Deol, Leoni Lekkakou, Ananth K Viswanath, Joseph M Pappachan
Diabesity-obesity resulting in diabetes-is a major health problem globally because of the obesity epidemic. Several anti-diabetic medications cause weight gain and may worsen obesity, and possibly diabeisty. Two recent small retrospective cohort studies showed weight loss and diabetes improvement with combination of glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose co-transporter type-2 (SGLT-2) inhibitors in obese subjects. We assessed the effect of combination therapy with GLP-1 agonists and SGLT-2 inhibitors in the management of diabesity in a retrospective study at the Wolverhampton Diabetes Centre...
September 30, 2016: Endocrine
https://www.readbyqxmd.com/read/27648144/exendin-4-protects-a%C3%AE-1-42-oligomer-induced-pc12-cell-apoptosis
#17
Chen Qiu, Yan-Ping Wang, Xiao-Dong Pan, Xiao-Ying Liu, Zhou Chen, Li-Bin Liu
BACKGROUND: Type 2 diabetes mellitus (T2DM) increases the risk of developing Alzheimer's disease. Most recently, GLP-1 analogs have been shown to have a significant neuroprotective role in several neurodegenerative diseases. However, few are known on its potential mechanism. OBJECTIVE: In this study, we report the effect of exendin-4 (Ex-4), a GLP-1 receptor agonist, on amyloid-β(1-42) peptide oligomer-induced apoptosis in a PC12 neuronal cell model. METHODS: MTT, DAPI and Annexin-V/PI assays revealed that the viability of PC12 cells decreased in a dose- and time-dependent manner after exposure to amyloid-β(1-42) oligomers...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27638877/glp-1-inhibits-vegfa-mediated-signaling-in-isolated-human-endothelial-cells-and-vegfa-induced-dilation-of-rat-mesenteric-arteries
#18
Cecilie Egholm, Makhala Michell Khammy, Thomas Dalsgaard, Aleksandra Mazur, Katerina Tritsaris, Anker Jon Hansen, Christian Aalkjaer, Steen Dissing
We investigated the acute effects of glucagon-like peptides-1 (GLP-1), GLP-1(1-36) and GLP-1(7-36) on vascular endothelial growth factor-A (VEGFA)-induced endothelium-dependent signaling and vasodilation. Our hypothesis was that GLP-1 released from intestinal L-cells modulates processes related to PLCγ activation, Src and eNOS signaling, thereby controlling endothelial vessel tone. By using RT-PCR we found mRNA for the GLP-1 receptor (GLP-1R) in human dermal microvascular endothelial cells (HDMEC), human retinal microvascular endothelial cells (HRMEC) and rat arteries...
September 16, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27610615/oral-delivery-of-pentameric-glucagon-like-peptide-1-by-recombinant-lactobacillus-in-diabetic-rats
#19
Yin Lin, Kasper Krogh-Andersen, Julien Pelletier, Harold Marcotte, Claes-Göran Östenson, Lennart Hammarström
Glucagon-like peptide-1 (GLP-1) is an incretin hormone produced by intestinal cells and stimulates insulin secretion from the pancreas in a glucose-dependent manner. Exogenously supplied GLP-1 analogues are used in the treatment of type 2 diabetes. An anti-diabetic effect of Lactobacillus in lowering plasma glucose levels and its use as a vehicle for delivery of protein and antibody fragments has been shown previously. The aim of this study was to employ lactobacilli as a vehicle for in situ production and delivery of GLP-1 analogue to normalize blood glucose level in diabetic GK (Goto-Kakizaki) rats...
2016: PloS One
https://www.readbyqxmd.com/read/27566229/glp-1-analogue-recovers-impaired-insulin-secretion-from-human-islets-treated-with-palmitate-via-down-regulation-of-socs2
#20
Azazul Islam Chowdhury, Peter Bergsten
Elevated circulating palmitate levels have been connected with type 2 diabetes mellitus. GLP-1 has favorable effects on beta-cells function. The aim was to identify mechanisms for decreased GSIS after long-term palmitate exposure and restoration by GLP-1 by analyzing changes in G-protein coupled receptor (GPCR) pathway signaling. Insulin secretory response to 20 mM glucose was attenuated after 7 days in islets exposed to palmitate but inclusion of exendin-4 restored secretion. Palmitate treatment altered genes of several GPCR signaling pathways including inflammatory pathways with up-regulated IL-1B, SOCS1 and SOCS2 transcript levels...
August 23, 2016: Molecular and Cellular Endocrinology
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