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https://www.readbyqxmd.com/read/29671019/lixisenatide-a-novel-glp-1-analog-protects-against-cerebral-ischemia-reperfusion-injury-in-diabetic-rats
#1
Rania G Abdel-Latif, Gehan H Heeba, Ashraf Taye, Mohamed M A Khalifa
Type 2 diabetes mellitus (T2DM) is a major risk factor for ischemic stroke accompanied by vascular dysfunction and poor cerebrovascular outcome. Lixisenatide is a glucagon like peptide-1 (GLP-1) analog that is recently used for T2DM treatment with established neuroprotective properties. This study investigated and compared the neuroprotective effect of lixisenatide against glimepiride on diabetic rats subjected to global cerebral ischemia/reperfusion (I/R) injury. T2DM-induced adult male Wistar rats were administered lixisenatide or glimepiride prior to induction of global cerebral I/R-induced injury...
April 18, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29473979/a-novel-glp-1-gip-gcg-triagonist-reduces-cognitive-deficits-and-pathology-in-the-3xtg-mouse-model-of-alzheimer-s-disease
#2
Tian Li, Juan-Juan Jiao, Christian Hölscher, Mei-Na Wu, Jun Zhang, Jia-Qing Tong, Xue-Fan Dong, Xue-Song Qu, Yue Cao, Hong-Yan Cai, Qiang Su, Jin-Shun Qi
Type 2 diabetes mellitus (T2DM) is an important risk factor for Alzheimer's disease (AD). Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have been identified to be effective in T2DM treatment and neuroprotection. In the present study, we further explored the effects of a novel unimolecular GLP-1/GIP/Gcg triagonist on the cognitive behavior and cerebral pathology in the 7-month-old triple transgenic mouse model of AD (3xTg-AD), and investigated its possible electrophysiological and molecular mechanisms...
February 23, 2018: Hippocampus
https://www.readbyqxmd.com/read/29435980/the-diabetes-drug-liraglutide-reverses-cognitive-impairment-in-mice-and-attenuates-insulin-receptor-and-synaptic-pathology-in-a-non-human-primate-model-of-alzheimer-s-disease
#3
Andre F Batista, Leticia Forny-Germano, Julia R Clarke, Natalia M Lyra E Silva, Jordano Brito-Moreira, Susan E Boehnke, Andrew Winterborn, Brian C Coe, Ann Lablans, Juliana F Vital, Suelen A Marques, Ana Mb Martinez, Matthias Gralle, Christian Holscher, William L Klein, Jean-Christophe Houzel, Sergio T Ferreira, Douglas P Munoz, Fernanda G De Felice
Alzheimer's disease (AD) is a devastating neurological disorder that still lacks an effective treatment, and this has stimulated an intense pursuit of disease-modifying therapeutics. Given the increasingly recognized link between AD and defective brain insulin signaling, we investigated the actions of liraglutide, a glucagon-like peptide-1 (GLP-1) analog marketed for treatment of type 2 diabetes, in experimental models of AD. Insulin receptor pathology is an important feature of AD brains that impairs the neuroprotective actions of central insulin signaling...
May 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29411931/neuroprotective-mechanisms-of-glucagon-like-peptide-1-based-therapies-in-ischaemic-stroke-a-systematic-review-based-on-pre-clinical-studies
#4
Ida R Marlet, Joakim N E Ölmestig, Tina Vilsbøll, Jørgen Rungby, Christina Kruuse
Glucagon-like peptide-1 (GLP-1)-based therapies, GLP-1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase-4 inhibitors (DPP-4Is) are widely used for the treatment of type 2 diabetes. Increasing evidence suggests that they may provide neuroprotection. The aim of this MiniReview was to systematically evaluate the proposed mechanism of action for GLP-1-based therapies in ischaemic brain damage in animals. We performed a literature search using Medline, Embase and The Cochrane Library. GLP-1-based therapies administered before, during or after experimental stroke in diabetic and non-diabetic animals were evaluated...
February 7, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29395648/delayed-administration-of-the-glucagon-like-peptide-1-analog-liraglutide-promoting-angiogenesis-after-focal-cerebral-ischemia-in-mice
#5
Yanxia Chen, Xiangjian Zhang, Junna He, Yanzhao Xie, Yang Yang
BACKGROUND: Glucagon-like peptide 1 (GLP-1) analogs administered before or after cerebral ischemia have been shown to provide neuroprotection. Here, we explored whether delayed administration of a GLP-1 analog, liraglutide, could improve long-term functional recovery and promote angiogenesis after stroke. MATERIALS AND METHODS: In the present study, mice were established as a focal cerebral cortical ischemia model and were intraperitoneally administered liraglutide or normal saline (NS) daily for 14 consecutive days, starting 1 day after cerebral ischemia...
January 21, 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/29274367/the-effects-of-incretin-hormones-on-cerebral-glucose-metabolism-in-health-and-disease
#6
REVIEW
Malin Nilsson, Albert Gjedde, Birgitte Brock, Michael Gejl, Jørgen Rungby
Incretin hormones, notably glucagon-like peptide-1 (GLP-1), are gluco-regulatory hormones with pleiotropic effects also in the central nervous system. Apart from a local production of GLP-1, systemic administration of the hormone has been shown to influence a number of cerebral pathologies, including neuroinflammation. Given the brains massive dependence on glucose as its major fuel, we here review the mechanistics of cerebral glucose transport and metabolism, focusing on the deleterious effects of both hypo- and hyperglycaemia...
December 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29235507/blood-brain-glucose-transfer-in-alzheimer-s-disease-effect-of-glp-1-analog-treatment
#7
Michael Gejl, Birgitte Brock, Lærke Egefjord, Kim Vang, Jørgen Rungby, Albert Gjedde
There are fewer than normal glucose transporters at the blood-brain barrier (BBB) in Alzheimer's disease (AD). When reduced expression of transporters aggravates the symptoms of AD, the transporters become a potential target of therapy. The incretin hormone GLP-1 prevents the decline of cerebral metabolic rate for glucose (CMRglc ) in AD, and GLP-1 may serve to raise transporter numbers. We hypothesized that the GLP-1 analog liraglutide would prevent the decline of CMRglc in AD by raising blood-brain glucose transfer, depending on the duration of disease...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29193450/clostridium-butyricum-exerts-a-neuroprotective-effect-in-a-mouse-model-of-traumatic-brain-injury-via-the-gut-brain-axis
#8
H Li, J Sun, J Du, F Wang, R Fang, C Yu, J Xiong, W Chen, Z Lu, J Liu
BACKGROUND: Traumatic brain injury (TBI) is a common occurrence following gastrointestinal dysfunction. Recently, more and more attentions are being focused on gut microbiota in brain and behavior. Glucagon-like peptide-1 (GLP-1) is considered as a mediator that links the gut-brain axis. The aim of this study was to explore the neuroprotective effects of Clostridium butyricum (Cb) on brain damage in a mouse model of TBI. METHODS: Male C57BL/6 mice were subjected to a model of TBI-induced by weight-drop impact head injury and were treated intragastrically with Cb...
November 27, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29170452/liraglutide-restores-chronic-er-stress-autophagy-impairments-and-apoptotic-signalling-in-sh-sy5y-cells
#9
Theodora Panagaki, Maria Michael, Christian Hölscher
Growing evidence suggests that agonists of glucagon-like peptide (GLP-1) receptor exert neuroprotective and neurorestorative effects across a range of experimental models of neuronal degeneration, and, recently, a pilot clinical trial of Liraglutide in Alzheimer's disease patients showed improvements in cerebral glucose consumption that signifies disease progression. However, the exact underlying mechanism of action remains unclear. Chronic endoplasmic reticulum (ER) stress has recently emerged as a mechanism for neuronal injury, rendering it a potent therapeutic target for acute and chronic neurodegenerative disorders...
November 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28991675/sodium-butyrate-exerts-protective-effect-against-parkinson-s-disease-in-mice-via-stimulation-of-glucagon-like-peptide-1
#10
Jiaming Liu, Fangyan Wang, Suzhi Liu, Jimei Du, Xuezhen Hu, Jiaojiao Xiong, Renchi Fang, Wenqian Chen, Jing Sun
Sodium butyrate (NaB) has exhibited protective activity in neurological disorders. Here, we investigated the neuroprotective effect and potential mechanisms of NaB in a mouse model of Parkinson's disease (PD). A mouse was intraperitoneally treated with MPTP (30mg/kg) for 7 consecutive days to induce PD model and NaB (200mg/kg) was intragastrically treated for 3weeks. The behavioral tests were then conducted. Dopaminergic degeneration was evaluated by western blot and immunohistochemistry of tyrosine hydroxylase (TH) in the SN...
October 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28912645/anti-inflammatory-effect-of-glucagon-like-peptide-1-receptor-agonist-exendin-4-through-modulation-of-ib1-jip1-expression-and-jnk-signaling-in-stroke
#11
Soojin Kim, Jaewon Jeong, Hye-Seon Jung, Bokyung Kim, Ye-Eun Kim, Da-Sol Lim, So-Dam Kim, Yun Seon Song
Glucagon like peptide-1 (GLP-1) stimulates glucose-dependent insulin secretion. Dipeptidyl peptidase-4 (DPP-4) inhibitors, which block inactivation of GLP-1, are currently in clinical use for type 2 diabetes mellitus. Recently, GLP-1 has also been reported to have neuroprotective effects in cases of cerebral ischemia. We therefore investigated the neuroprotective effects of GLP-1 receptor (GLP-1R) agonist, exendin-4 (ex-4), after cerebral ischemia-reperfusion injury. Transient middle cerebral artery occlusion (tMCAO) was induced in rats by intracerebroventricular (i...
August 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28456941/activation-of-glucagon-like-peptide-1-receptor-promotes-neuroprotection-in-experimental-autoimmune-encephalomyelitis-by-reducing-neuroinflammatory-responses
#12
Chi-Ho Lee, Se Jin Jeon, Kyu Suk Cho, Eunjung Moon, Arjun Sapkota, Hee Sook Jun, Jong Hoon Ryu, Ji Woong Choi
The signaling axis of glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) has been an important component in overcoming diabetes, and recent reports have uncovered novel beneficial roles of this signaling axis in central nervous system (CNS) disorders, such as Alzheimer's disease, Parkinson's disease, and cerebral ischemia, accelerating processes for exendin-4 repositioning. Here, we studied whether multiple sclerosis (MS) could be a complement to the CNS disorders that are associated with the GLP-1/GLP-1R signaling axis...
April 29, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28342971/a-novel-dual-glp-1-gip-receptor-agonist-alleviates-cognitive-decline-by-re-sensitizing-insulin-signaling-in-the-alzheimer-icv-stz-rat-model
#13
Lijuan Shi, Zhihua Zhang, Lin Li, Christian Hölscher
Alzheimer's disease (AD) is a progressive neurodegenerative disorder, accompanied by memory loss and cognitive impairments, and there is no effective treatment for it at present. Since type 2 diabetes (T2DM) has been identified as a risk factor for AD, the incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP), promising antidiabetic agents for the treatment of type 2 diabetes, have been tested in models of neurodegenerative disease including AD and achieved good results...
June 1, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28122257/delayed-administration-of-the-glp-1-receptor-agonist-liraglutide-improves-metabolic-and-functional-recovery-after-cerebral-ischemia-in-rats
#14
Wenbin Dong, Yunping Miao, Aiying Chen, Min Cheng, Xiaodi Ye, Fahuan Song, Gaoli Zheng
Glucagon-like peptide 1 receptor (GLP-1R) agonists administered before or immediately after induction of experimental stroke have been shown to provide acute neuroprotection. Here, we determined whether delayed treatment with a GLP-1R agonist could improve metabolic and functional recovery after stroke. Rats were subjected to middle cerebral artery occlusion (MCAO) and given the well-established GLP-1R agonist liraglutide (50, 100, or 200μg/kg) or normal saline (NS) daily for 4 weeks, starting 1 day after MCAO...
February 22, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/27871675/glucagon-like-peptide-1-and-the-central-peripheral-nervous-system-crosstalk-in-diabetes
#15
REVIEW
Giovanna Muscogiuri, Ralph A DeFronzo, Amalia Gastaldelli, Jens J Holst
Glucagon-like peptide-1 (GLP-1) is released in response to meals and exerts important roles in the maintenance of normal glucose homeostasis. GLP-1 is also important in the regulation of neurologic and cognitive functions. These actions are mediated via neurons in the nucleus of the solitary tract that project to multiple regions expressing GLP-1 receptors (GLP-1Rs). Treatment with GLP-1R agonists (GLP-1-RAs) reduces ischemia-induced hyperactivity, oxidative stress, neuronal damage and apoptosis, cerebral infarct volume, and neurologic damage, after cerebral ischemia, in experimental models...
February 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/27856285/neurotrophic-and-neuroprotective-effects-of-oxyntomodulin-in-neuronal-cells-and-a-rat-model-of-stroke
#16
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...
February 2017: Experimental Neurology
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...
August 26, 2016: Journal of Neuroinflammation
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
#18
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...
August 24, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27496691/glp-1-and-estrogen-conjugate-acts-in-the-supramammillary-nucleus-to-reduce-food-reward-and-body-weight
#19
Heike Vogel, Stefanie Wolf, Cristina Rabasa, Francisca Rodriguez-Pacheco, Carina S Babaei, Franziska Stöber, Jürgen Goldschmidt, Richard D DiMarchi, Brian Finan, Matthias H Tschöp, Suzanne L Dickson, Annette Schürmann, Karolina P Skibicka
The obesity epidemic continues unabated and currently available pharmacological treatments are not sufficiently effective. Combining gut/brain peptide, GLP-1, with estrogen into a conjugate may represent a novel, safe and potent, strategy to treat diabesity. Here we demonstrate that the central administration of GLP-1-estrogen conjugate reduced food reward, food intake, and body weight in rats. In order to determine the brain location of the interaction of GLP-1 with estrogen, we avail of single-photon emission computed tomography imaging of regional cerebral blood flow and pinpoint a brain site unexplored for its role in feeding and reward, the supramammillary nucleus (SUM) as a potential target of the conjugated GLP-1-estrogen...
November 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27421117/long-term-treatment-with-liraglutide-a-glucagon-like-peptide-1-glp-1-receptor-agonist-has-no-effect-on-%C3%AE-amyloid-plaque-load-in-two-transgenic-app-ps1-mouse-models-of-alzheimer-s-disease
#20
Henrik H Hansen, Katrine Fabricius, Pernille Barkholt, Pernille Kongsbak-Wismann, Chantal Schlumberger, Jacob Jelsing, Dick Terwel, Annelies Termont, Charles Pyke, Lotte Bjerre Knudsen, Niels Vrang
One of the major histopathological hallmarks of Alzheimer's disease (AD) is cerebral deposits of extracellular β-amyloid peptides. Preclinical studies have pointed to glucagon-like peptide 1 (GLP-1) receptors as a potential novel target in the treatment of AD. GLP-1 receptor agonists, including exendin-4 and liraglutide, have been shown to promote plaque-lowering and mnemonic effects of in a number of experimental models of AD. Transgenic mouse models carrying genetic mutations of amyloid protein precursor (APP) and presenilin-1 (PS1) are commonly used to assess the pharmacodynamics of potential amyloidosis-lowering and pro-cognitive compounds...
2016: PloS One
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