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https://www.readbyqxmd.com/read/27871675/glucagon-like-peptide-1-and-the-central-peripheral-nervous-system-crosstalk-in-diabetes
#1
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...
October 27, 2016: 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
#2
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/27566245/the-glucagon-like-peptide-1-receptor-agonist-exendin-4-ameliorates-warfarin-associated-hemorrhagic-transformation-after-cerebral-ischemia
#3
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/27554094/glucagon-like-peptide-1-analogue-liraglutide-in-experimental-cerebral-malaria-implications-for-the-role-of-oxidative-stress-in-cerebral-malaria
#4
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/27496691/glp-1-and-estrogen-conjugate-acts-in-the-supramammillary-nucleus-to-reduce-food-reward-and-body-weight
#5
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
#6
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
https://www.readbyqxmd.com/read/27296974/the-glp-1-receptor-agonists-exendin-4-and-liraglutide-alleviate-oxidative-stress-and-cognitive-and-micturition-deficits-induced-by-middle-cerebral-artery-occlusion-in-diabetic-mice
#7
Ping-Chia Li, Li-Fen Liu, Ming-Jia Jou, Hao-Kuang Wang
BACKGROUND: Glucagon-like peptide 1 (GLP-1) analogs protect a variety of cell types against oxidative damage and vascular and neuronal injury via binding to GLP-1 receptors. This study aimed to investigate the effects of the GLP-1 analogs exendin-4 and liraglutide on cerebral blood flow, reactive oxygen species production, expression of oxidative stress-related proteins, cognition, and pelvic sympathetic nerve-mediated bladder contraction after middle cerebral artery occlusion (MCAO) injury in the db/db mouse model of diabetes...
2016: BMC Neuroscience
https://www.readbyqxmd.com/read/27240461/the-neuroprotection-of-liraglutide-against-ischaemia-induced-apoptosis-through-the-activation-of-the-pi3k-akt-and-mapk-pathways
#8
Huili Zhu, Yusheng Zhang, Zhongshan Shi, Dan Lu, Tingting Li, Yan Ding, Yiwen Ruan, Anding Xu
Glucagon-like peptide-1 (GLP-1) is an incretin hormone that increases glucose-dependent insulin secretion to reduce the glucose level. Liraglutide, a long-acting GLP-1 analogue, has been found to have neuroprotective action in various experimental models. However, the protective mechanisms of liraglutide in ischaemic stroke remain unclear. Here, we demonstrated that liraglutide significantly decreased the infarct volume, improved neurologic deficits, and lowered stress-related hyperglycaemia without causing hypoglycaemia in a rat model of middle cerebral artery occlusion (MCAO)...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27207082/cerebral-cortex-a-target-and-source-of-insulin
#9
REVIEW
Éva A Csajbók, Gábor Tamás
Recent results suggest that insulin is synthesised by a subpopulation of neurons in the cerebral cortex and neural progenitor cells of the hippocampus. Supplementing the slow supply of insulin to the brain by pancreatic beta cells, the insulin locally released by neurons provides a rapid means of regulating local microcircuits, effectively modulating synaptic transmission and on-demand energy homeostasis of neural networks. Modulation of insulin production by brain neurons via glucagon-like peptide 1 (GLP-1) agonists might be useful in counteracting diabetes, obesity and neurodegenerative diseases...
August 2016: Diabetologia
https://www.readbyqxmd.com/read/26922186/postprandial-glp-1-secretion-after-bariatric-surgery-in-three-cases-of-severe-obesity-related-to-craniopharyngiomas
#10
Marion Bretault, Suzanne Laroche, Jean-Marc Lacorte, Charles Barsamian, Michel Polak, Marie-Laure Raffin-Sanson, Philippe Touraine, Jean-Luc Bouillot, Sebastien Czernichow, Claire Carette
Craniopharyngiomas are rare cerebral tumors associated with severe obesity after hypothalamic surgery. A meta-analysis showed significant weight loss at 1 year after bariatric surgery in these patients even though more modest than in common causes of obesity. We hypothesized that this discrepancy could be partly explained by differences in GLP-1 secretion after surgery since patients with craniopharyngioma present a significantly higher degree of insulin resistance and hyperinsulinism than common obese control...
May 2016: Obesity Surgery
https://www.readbyqxmd.com/read/26863436/an-orally-active-allosteric-glp-1-receptor-agonist-is-neuroprotective-in-cellular-and-rodent-models-of-stroke
#11
Huinan Zhang, Yunhan Liu, Shaoyu Guan, Di Qu, Ling Wang, Xinshang Wang, Xubo Li, Shimeng Zhou, Ying Zhou, Ning Wang, Jingru Meng, Xue Ma
Diabetes is a major risk factor for the development of stroke. Glucagon-like peptide-1 receptor (GLP-1R) agonists have been in clinical use for the treatment of diabetes and also been reported to be neuroprotective in ischemic stroke. The quinoxaline 6,7-dichloro-2-methylsulfonyl-3-N-tert- butylaminoquinoxaline (DMB) is an agonist and allosteric modulator of the GLP-1R with the potential to increase the affinity of GLP-1 for its receptor. The aim of this study was to evaluate the neuroprotective effects of DMB on transient focal cerebral ischemia...
2016: PloS One
https://www.readbyqxmd.com/read/26828649/effects-of-incretin-based-therapies-on-neuro-cardiovascular-dynamic-changes-induced-by-high-fat-diet-in-rats
#12
Silvio Rodrigues Marques-Neto, Raquel Carvalho Castiglione, Aiza Pontes, Dahienne Ferreira Oliveira, Emanuelle Baptista Ferraz, José Hamilton Matheus Nascimento, Eliete Bouskela
BACKGROUND AND AIMS: Obesity promotes cardiac and cerebral microcirculatory dysfunction that could be improved by incretin-based therapies. However, the effects of this class of compounds on neuro-cardiovascular system damage induced by high fat diet remain unclear. The aim of this study was to investigate the effects of incretin-based therapies on neuro-cardiovascular dysfunction induced by high fat diet in Wistar rats. METHODS AND RESULTS: We have evaluated fasting glucose levels and insulin resistance, heart rate variability quantified on time and frequency domains, cerebral microcirculation by intravital microscopy, mean arterial blood pressure, ventricular function and mitochondrial swelling...
2016: PloS One
https://www.readbyqxmd.com/read/26683903/pharmacologic-stimulation-of-central-glp-1-receptors-has-opposite-effects-on-the-alterations-of-plasma-fgf21-levels-induced-by-feeding-and-fasting
#13
Katsunori Nonogaki, Takao Kaji, Tomoe Yamazaki, Mari Murakami
Fibroblast growth factor 21 (FGF21) functions as an endocrine hormone to regulate energy metabolism. Circulating FGF21 is derived from the liver and is produced in response to alterations of nutritional status. Here we show the effects of liraglutide, a human glucagon-like-peptide-1 (GLP-1) receptor agonist, injected into the third cerebral ventricle on body weight and plasma FGF21 levels in free-feeding mice, food-deprived mice, and mice provided 1g after the injection. In free-feeding mice, liraglutide (5-100μg/kg) injected into the third cerebral ventricle suppressed food intake and body weight after 24h in a dose-dependent manner...
January 26, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/26666230/novel-glp-1-glucagon-like-peptide-1-analogues-and-insulin-in-the-treatment-for-alzheimer-s-disease-and-other-neurodegenerative-diseases
#14
REVIEW
Valeria Calsolaro, Paul Edison
The link between diabetes mellitus and Alzheimer's disease (AD) has been known for the last few decades. Since insulin and insulin receptors are known to be present in the brain, the downstream signalling as well as the effect of hyperinsulinemia have been extensively studied in both AD and Parkinson's disease. Glucagon-like peptide-1 (GLP-1) is a hormone belonging to the incretin family, and its receptors (GLP-1Rs) can be found in pancreatic cells and in vascular endothelium. Interestingly, GLP-1Rs are found in the neuronal cell body and dendrites in the central nervous system (CNS), in particular in the hypothalamus, hippocampus, cerebral cortex and olfactory bulb...
December 2015: CNS Drugs
https://www.readbyqxmd.com/read/26555034/a-novel-dual-glucagon-like-peptide-1-and-glucose-dependent-insulinotropic-polypeptide-receptor-agonist-is-neuroprotective-in-transient-focal-cerebral-ischemia-in-the-rat
#15
COMPARATIVE STUDY
Ling Han, Christian Hölscher, Guo-Fang Xue, Guanglai Li, Dongfang Li
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists have been shown to be neuroprotective in previous studies in animal models of Alzheimer's or Parkinson's disease. Recently, novel dual-GLP-1/GIP receptor agonists that activate both receptors (DA) were developed to treat diabetes. We tested the protective effects of a novel potent DA against middle cerebral artery occlusion injury in rats and compared it with a potent GLP-1 analog, Val(8)-GLP-1(glu-PAL)...
January 6, 2016: Neuroreport
https://www.readbyqxmd.com/read/26546042/peptidic-exenatide-and-herbal-catalpol-mediate-neuroprotection-via-the-hippocampal-glp-1-receptor-%C3%AE-endorphin-pathway
#16
Yu Jia, Nian Gong, Teng-Fei Li, Bin Zhu, Yong-Xiang Wang
Both peptidic agonist exenatide and herbal agonist catalpol of the glucagon-like peptide-1 receptor (GLP-1R) are neuroprotective. We have previously shown that activation of spinal GLP-1Rs expresses β-endorphin in microglia to produce antinociception. The aim of this study was to explore whether exenatide and catalpol exert neuroprotection via activation of the hippocampal GLP-1R/β-endorphin pathway. The rat middle cerebral artery occlusion model was employed, and the GLP-1R immunofluorescence staining and β-endorphin measurement were assayed in the hippocampus and primary cultures of microglia, neurons and astrocytes...
December 2015: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/26382859/de-novo-arteriovenous-malformation-growth-secondary-to-implantation-of-genetically-modified-allogeneic-mesenchymal-stem-cells-in-the-brain
#17
Makoto Nakamura, Amir Samii, Josef M Lang, Friedrich Götz, Madjid Samii, Joachim K Krauss
BACKGROUND AND IMPORTANCE: Local biological drug delivery in the brain is an innovative field of medicine that developed rapidly in recent years. Our report illustrates a unique case of de novo development of a cerebral arteriovenous malformation (AVM) after implantation of genetically modified allogeneic mesenchymal stem cells in the brain. CLINICAL PRESENTATION: A 50-year-old man was included in a prospective clinical study (study ID number CM GLP-1/01, 2007-004516-31) investigating a novel neuroprotective approach in stroke patients to prevent perihematomal neuronal damage...
April 2016: Neurosurgery
https://www.readbyqxmd.com/read/26116695/exenatide-regulates-cerebral-glucose-metabolism-in-brain-areas-associated-with-glucose-homeostasis-and-reward-system
#18
RANDOMIZED CONTROLLED TRIAL
Giuseppe Daniele, Patricia Iozzo, Marjorie Molina-Carrion, Jack Lancaster, Demetrio Ciociaro, Eugenio Cersosimo, Devjit Tripathy, Curtis Triplitt, Peter Fox, Nicolas Musi, Ralph DeFronzo, Amalia Gastaldelli
Glucagon-like peptide 1 receptors (GLP-1Rs) have been found in the brain, but whether GLP-1R agonists (GLP-1RAs) influence brain glucose metabolism is currently unknown. The study aim was to evaluate the effects of a single injection of the GLP-1RA exenatide on cerebral and peripheral glucose metabolism in response to a glucose load. In 15 male subjects with HbA1c of 5.7 ± 0.1%, fasting glucose of 114 ± 3 mg/dL, and 2-h glucose of 177 ± 11 mg/dL, exenatide (5 μg) or placebo was injected in double-blind, randomized fashion subcutaneously 30 min before an oral glucose tolerance test (OGTT)...
October 2015: Diabetes
https://www.readbyqxmd.com/read/26058696/exendin-4-loaded-plga-microspheres-relieve-cerebral-ischemia-reperfusion-injury-and-neurologic-deficits-through-long-lasting-bioactivity-mediated-phosphorylated-akt-enos-signaling-in-rats
#19
Chiang-Ting Chien, Ming-Jia Jou, Tai-Yu Cheng, Chih-Hui Yang, Tzu-Ying Yu, Ping-Chia Li
Glucagon-like peptide-1 (GLP-1) receptor activation in the brain provides neuroprotection. Exendin-4 (Ex-4), a GLP-1 analog, has seen limited clinical usage because of its short half-life. We developed long-lasting Ex-4-loaded poly(D,L-lactide-co-glycolide) microspheres (PEx-4) and explored its neuroprotective potential against cerebral ischemia in diabetic rats. Compared with Ex-4, PEx-4 in the gradually degraded microspheres sustained higher Ex-4 levels in the plasma and cerebrospinal fluid for at least 2 weeks and improved diabetes-induced glycemia after a single subcutaneous administration (20 μg/day)...
November 2015: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/25822252/preservation-of-the-blood-brain-barrier-and-cortical-neuronal-tissue-by-liraglutide-a-long-acting-glucagon-like-1-analogue-after-experimental-traumatic-brain-injury
#20
Jakob Hakon, Karsten Ruscher, Bertil Romner, Gregor Tomasevic
Cerebral edema is a common complication following moderate and severe traumatic brain injury (TBI), and a significant risk factor for development of neuronal death and deterioration of neurological outcome. To this date, medical approaches that effectively alleviate cerebral edema and neuronal death after TBI are not available. Glucagon-like peptide-1 (GLP-1) has anti-inflammatory properties on cerebral endothelium and exerts neuroprotective effects. Here, we investigated the effects of GLP-1 on secondary injury after moderate and severe TBI...
2015: PloS One
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