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https://www.readbyqxmd.com/read/27856285/neurotrophic-and-neuroprotective-effects-of-oxyntomodulin-in-neuronal-cells-and-a-rat-model-of-stroke
#1
Yazhou Li, Kou-Jen Wu, Seong-Jin Yu, Ian A Tamargo, Yun Wang, Nigel H Greig
Proglucagon-derived peptides, especially glucagon-like peptide-1 (GLP-1) and its long-acting mimetics, have exhibited neuroprotective effects in animal models of stroke. Several of these peptides are in clinical trials for stroke. Oxyntomodulin (OXM) is a proglucagon-derived peptide that co-activates the GLP-1 receptor (GLP-1R) and the glucagon receptor (GCGR). The neuroprotective action of OXM, however, has not been thoroughly investigated. In this study, the neuroprotective effect of OXM was first examined in human neuroblastoma (SH-SY5Y) cells and rat primary cortical neurons...
November 14, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27782127/endogenous-glucagon-like-peptide-1-receptor-signaling-in-the-nucleus-tractus-solitarius-is-required-for-food-intake-control
#2
Amber L Alhadeff, Blake D Mergler, Derek J Zimmer, Christopher A Turner, David J Reiner, Heath D Schmidt, Harvey J Grill, Matthew R Hayes
Though the glucagon-like peptide-1 (GLP-1) system is critical to energy balance control and is a target for obesity pharmacotherapies, the receptor populations mediating effects of endogenous GLP-1 signaling are not fully understood. To address this, we developed a novel adeno-associated virus (AAV-GLP-1R) that utilizes short hairpin RNA to chronically knock down GLP-1 receptors (GLP-1R) in rats. Since pharmacological studies highlight the hindbrain nucleus tractus solitarius (NTS) as a brain region important for GLP-1R-mediated effects on energy balance, AAV-GLP-1R was injected into the NTS to examine the role of endogenous NTS GLP-1R signaling in energy balance control...
October 26, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27780892/diabetes-negatively-affects-cortical-and-striatal-gabaergic-neurons-an-effect-that-is-partially-counteracted-by-exendin-4
#3
Martin Larsson, Grazyna Lietzau, David Nathanson, Claes-Göran Östenson, Carina Mallard, Maria E Johansson, Thomas Nyström, Cesare Patrone, Vladimer Darsalia
Type 2 diabetic (T2D) patients often develop early cognitive and sensorimotor impairments. The pathophysiological mechanisms behind these problems are largely unknown. Recent studies demonstrate that dysfunctional γ-Aminobutyric acid (GABAergic) neurons are involved in age-related cognitive decline. We hypothesized that similar, but earlier dysfunction is taking place under T2D in the neocortex and striatum (two brain areas important for cognition and sensorimotor functions). We also hypothesized that the T2D-induced effects are pharmacologically reversible by anti-diabetic drugs targeting the glucagon-like peptide-1 receptor (GLP-1R)...
October 25, 2016: Bioscience Reports
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
#4
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/27766537/a-novel-bioresorbable-device-as-a-controlled-release-system-for-protecting-cells-from-oxidative-stress-from-alzheimer-s-disease
#5
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/27732058/vascular-biology-of-glucagon-receptor-superfamily-peptides-complexity-controversy-and-clinical-relevance
#6
Gemma Pujadas, Daniel J Drucker
Regulatory peptides produced in islet and gut endocrine cells, including glucagon, GLP-1, GLP-2, and GIP exert actions with considerable metabolic importance and translational relevance. Although the clinical development of GLP-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4(DPP4) inhibitors has fostered research into how these hormones act on the normal and diseased heart, less is known about the actions of these peptides on blood vessels. Here we review the effects of these peptide hormones on normal blood vessels, and highlight their vascular actions in the setting of experimental and clinical vascular injury...
October 12, 2016: Endocrine Reviews
https://www.readbyqxmd.com/read/27722184/the-physiological-role-of-the-brain-glp-1-system-in-stress
#7
Marie K Holt, Stefan Trapp
Glucagon-like peptide-1 (GLP-1) within the brain is a potent regulator of food intake and most studies have investigated the anorexic effects of central GLP-1. A range of brain regions have now been found to be involved in GLP-1 mediated anorexia, including some which are not traditionally associated with appetite regulation. However, a change in food intake can be indicative of not only reduced energy demand, but also changes in the organism's motivation to eat following stressful stimuli. In fact, acute stress is well-known to reduce food intake...
December 31, 2016: Cogent Biology
https://www.readbyqxmd.com/read/27715341/modulation-of-glp-1-signaling-as-a-novel-therapeutic-approach-in-the-treatment-of-alzheimer-s-disease-pathology
#8
Antonella Tramutola, Andrea Arena, Chiara Cini, D Allan Butterfield, Eugenio Barone
Clinical studies suggest a link between peripheral insulin resistance and cognitive dysfunction. Post-mortem analyses of Alzheimer disease (AD) subjects revealed insulin resistance in the brain, suggesting a role of this condition in cognitive deficits observed in AD. In this review, we focus on the glucagon-like peptide-1 (GLP-1) signaling pathway, whose role in the brain is collecting increasing attention because of its association with insulin signaling activation. Areas covered: The role of GLP-1-mediated effects in the brain and how they are affected along the progression of AD pathology is discussed...
October 7, 2016: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/27699599/linagliptin-a-dipeptidyl-peptidase-4-inhibitor-mitigates-cognitive-deficits-and-pathology-in-the-3xtg-ad-mouse-model-of-alzheimer-s-disease
#9
Jayasankar Kosaraju, R M Damian Holsinger, Lixia Guo, Kin Yip Tam
Glucagon-like peptide-1 (GLP-1) is an incretin hormone shown to be active in the treatment of type-2 diabetes (T2D) and has also been shown as efficacious in Alzheimer's disease (AD). Dipeptidyl peptidase-4 (DPP-4), an enzyme that is expressed in numerous cells, rapidly inactivates endogenous GLP-1. Therefore, DPP-4 inhibition is employed as a therapeutic avenue to increase GLP-1 levels in the management of T2D. The effectiveness of DPP-4 inhibitors in the treatment of AD has been reported in various animal models of AD...
October 3, 2016: Molecular Neurobiology
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
#10
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/27692857/insights-into-the-central-pathways-involved-in-the-emetic-and-behavioural-responses-to-exendin-4-in-the-ferret
#11
Zengbing Lu, Chi-Kong Yeung, Ge Lin, David T W Yew, P L R Andrews, John A Rudd
BACKGROUND: GLP-1 receptor agonists are utilised for the treatment of Type-2 diabetes but can be associated with undesirable effects of nausea and vomiting. OBJECTIVES: To investigate the role of GLP-1 receptors in mechanisms of emesis, behaviours indicative of nausea (BIN) and food intake in the ferret. RESULTS: Exendin-4 (10 and 30nmol, i.c.v.) induced emesis, inhibited food intake, and increased the frequency of BIN. Increases in c-Fos in the brainstem, midbrain and forebrain occurred in animals exhibiting emesis; no activation of the brainstem occurred in animals not vomiting...
September 14, 2016: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/27664588/influence-of-glucagon-like-peptide-2-on-energy-homeostasis
#12
REVIEW
Sara Baldassano, Antonella Amato, Flavia Mulè
Glucagon like peptide-2 (GLP-2) is a gastrointestinal hormone released from enteroendocrine L-type cells together with glucagon like peptide-1 in response to dietary nutrients. GLP-2 acts through a specific receptor, the GLP-2 receptor, mainly located in the gut and in the brain. Classically, GLP-2 is considered a trophic hormone involved in the maintenance of intestinal epithelial morphology and function. This role has been targeted for therapies promoting repair and adaptive growth of the intestinal mucosa...
December 2016: Peptides
https://www.readbyqxmd.com/read/27606348/erratum-glp-1-receptor-activation-improves-neurological-outcome-after-murine-brain-trauma-1-9-pp-1-12
#13
(no author information available yet)
[This corrects the article DOI: 10.1002/acn3.99.].
August 2016: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/27590359/apelin-36-is-protective-against-n-methyl-d-aspartic-acid-induced-retinal-ganglion-cell-death-in-the-mice
#14
Kenji Sakamoto, Yuta Murakami, Shohei Sawada, Hiroko Ushikubo, Asami Mori, Tsutomu Nakahara, Kunio Ishii
Retinal ganglion cell death in glaucoma is caused at least in part by a large Ca(2+) influx through N-methyl-D-aspartic acid (NMDA) receptors. Apelin is a peptide originally found in the tissue extracts of bovine stomach. Recent studies have been shown that apelin protects against the ischemic-reperfused injury in the brain. We examined whether apelin had protective effects on the NMDA-induced retinal ganglion cell (RGC) death using B6.Cg-TgN(Thy1-CFP)23Jrs/J transgenic mice, which express the enhanced cyan fluorescent protein in RGCs in the retina, in vivo...
August 31, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27580096/human-brain-responses-to-gastrointestinal-nutrients-and-gut-hormones
#15
John T McLaughlin, Shane McKie
Functional mapping of human brain activation has made it possible to understand how different nutrients in the gut impact on homeostatic and appetitive brain responses. Current data are limited, but nutrient-specific effects are observed, with differential responses to lipid and sugars. Responses are not a simple function of calorie intake. Gut hormones such as CCK, PYY, GLP-1 and ghrelin are implicated in these responses, but may not exert effects directly on the brain. Research is now addressing how these homeostatic signalling states (fasting/fed) interact with hedonic responses, such as those evoked by images of appealing food...
August 27, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27572131/pharmacological-actions-of-glucagon-like-peptide-1-gastric-inhibitory-polypeptide-and-glucagon
#16
R Sekar, K Singh, A W R Arokiaraj, B K C Chow
Glucagon family of peptide hormones is a group of structurally related brain-gut peptides that exert their pleiotropic actions through interactions with unique members of class B1 G protein-coupled receptors (GPCRs). They are key regulators of hormonal homeostasis and are important drug targets for metabolic disorders such as type-2 diabetes mellitus (T2DM), obesity, and dysregulations of the nervous systems such as migraine, anxiety, depression, neurodegeneration, psychiatric disorders, and cardiovascular diseases...
2016: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/27566245/the-glucagon-like-peptide-1-receptor-agonist-exendin-4-ameliorates-warfarin-associated-hemorrhagic-transformation-after-cerebral-ischemia
#17
Fangzhe Chen, Weifeng Wang, Hongyan Ding, Qi Yang, Qiang Dong, Mei Cui
BACKGROUND: As the number of patients with cardioembolic ischemic stroke is predicted to be double by 2030, increased burden of warfarin-associated hemorrhagic transformation (HT) after cerebral ischemia is an expected consequence. However, thus far, no effective treatment strategy is available for HT prevention in routine clinical practice. While the glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 (Ex-4) is known to protect against oxidative stress and neuronal cell death caused by ischemic brain damage, its effect on preventing warfarin-associated HT after cerebral ischemia is yet unknown...
2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27563837/single-dose-and-repeated-administrations-of-liraglutide-alter-energy-metabolism-in-the-brains-of-young-and-adult-rats
#18
Morgana Prá, Gabriela Kozuchovski Ferreira, Aline Haas de Mello, Rosiane de Bona Schraiber, Larissa Colonetti Cardoso, Luana da Rosa Souza, Naiana da Rosa, Jucélia Jeremias Fortunato, Gislaine Tezza Rezin
Liraglutide is a human glucagon-like peptide-1 (GLP-1) analogue that was recently approved to treat obesity in some countries. Considering that liraglutide effects on brain energy metabolism are little known, we evaluated the effects of liraglutide on the energy metabolism. Animals received a single or daily injection of saline or liraglutide during 7 days (25, 50, 100, or 300 μg/kg i.p.). Twenty-four hours after the single or last injection, the rats were euthanized and the hypothalamus, prefrontal cortex, cerebellum, hippocampus, striatum, and posterior cortex were isolated...
October 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/27554094/glucagon-like-peptide-1-analogue-liraglutide-in-experimental-cerebral-malaria-implications-for-the-role-of-oxidative-stress-in-cerebral-malaria
#19
Brian DellaValle, Casper Hempel, Trine Staalsoe, Flemming Fryd Johansen, Jørgen Anders Lindholm Kurtzhals
BACKGROUND: Cerebral malaria from Plasmodium falciparum infection is major cause of death in the tropics. The pathogenesis of the disease is complex and the contribution of reactive oxygen and nitrogen species (ROS/RNS) in the brain is incompletely understood. Insulinotropic glucagon-like peptide-1 (GLP-1) mimetics have potent neuroprotective effects in animal models of neuropathology associated with ROS/RNS dysfunction. This study investigates the effect of the GLP-1 analogue, liraglutide against the clinical outcome of experimental cerebral malaria (ECM) and Plasmodium falciparum growth...
2016: Malaria Journal
https://www.readbyqxmd.com/read/27521218/potential-effects-of-current-drug-therapies-on-cognitive-impairment-in-patients-with-type-2-diabetes
#20
REVIEW
Caterina Palleria, Christian Leporini, Francesca Maida, Elena Succurro, Giovambattista De Sarro, Franco Arturi, Emilio Russo
Type 2 diabetes mellitus is a complex metabolic disease that can cause serious damage to various organs. Among the best-known complications, an important role is played by cognitive impairment. Impairment of cognitive functioning has been reported both in type 1 and 2 diabetes mellitus. While this comorbidity has long been known, no major advances have been achieved in clinical research; it is clear that appropriate control of blood glucose levels represents the best current (although unsatisfactory) approach in the prevention of cognitive impairment...
July 2016: Frontiers in Neuroendocrinology
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