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GLP-1 Neuroprotection

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https://www.readbyqxmd.com/read/28611211/metabolic-and-neuroprotective-effects-of-dapagliflozin-and-liraglutide-in-diabetic-mice
#1
Paul Millar, Nupur Pathak, Vadivel Parthsarathy, Tony Bjourson, Maurice O'Kane, Varun Pathak, R Charlotte Moffett, Peter R Flatt, Victor A Gault
This study assessed the metabolic and neuroprotective actions of the sodium glucose co-transporter-2 inhibitor dapagliflozin in combination with the GLP-1 agonist liraglutide in dietary-induced diabetic mice. Mice administered low-dose streptozotocin (STZ) on a high fat diet received dapagliflozin, liraglutide, dapagliflozin-plus-liraglutide (DAPA-Lira) or vehicle once-daily over 28 days. Energy intake, body weight, glucose and insulin concentrations were measured at regular intervals. Glucose tolerance, insulin sensitivity, hormone and biochemical analysis, dual-energy x-ray absorptiometry densitometry, novel object recognition, islet and brain histology were examined...
June 13, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28456941/activation-of-glucagon-like-peptide-1-receptor-promotes-neuroprotection-in-experimental-autoimmune-encephalomyelitis-by-reducing-neuroinflammatory-responses
#2
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/28447569/a-new-treatment-strategy-for-parkinson-s-disease-through-the-gut-brain-axis-the-glucagon-like-peptide-1-receptor-pathway
#3
Dong Seok Kim, Ho-Il Choi, Yun Wang, Yu Luo, Barry J Hoffer, Nigel H Greig
Molecular communications in the gut-brain axis, between the central nervous system and the gastrointestinal tract, arecritical for maintaining healthy brain function particularly in aging. Epidemiological analyses indicate type 2 diabetes mellitus (T2DM) is a risk factor for neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's diseases (PD) for which aging shows a major correlative association. Common pathophysiological features exist between T2DM, AD and PD, including oxidative stress, inflammation, insulin resistance, abnormal protein processing and cognitive decline, and suggest that effective drugs for T2DM that positively impact the gut-brain axis could provide an effective treatment option for neurodegenerative diseases...
April 26, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28435972/-glp-1-gip-gcg-receptor-triagonist-improves-the-cognitive-behaviors-in-triple-transgenic-mice-of-alzheimer-s-disease
#4
Juan-Juan Jiao, Christian Hölscher, Tian Li, Xue-Fan Dong, Xue-Song Qu, Yue Cao, Mei-Na Wu, Zhao-Jun Wang, Jin-Shun Qi
Alzheimer's disease (AD) is a progressively neurodegenerative disorder, which seriously affects human health but is still irreversible up to now. Recent studies indicate that type 2 diabetes mellitus (T2DM) is an important risk factor for AD, and the drugs used for treatment of T2DM have shown some neuroprotective effects in the treatment of AD. Glucagon-like peptide-1 (GLP-1)/ glucose-dependent insulinotropic polypeptide (GIP)/glucagon (Gcg) receptor Triagonist is a new monomeric polypeptide equally activating the GLP-1/GIP/Gcg receptors, which is built on the basis of GLP-1/Gcg receptor coagonist core sequence, and incorporated with partial amino acids of GIP...
April 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28387682/exendin-4-treatment-improves-lps-induced-depressive-like-behavior-without-affecting-pro-inflammatory-cytokines
#5
Filip Ventorp, Cecilie Bay-Richter, Analise Sauro Nagendra, Shorena Janelidze, Viktor Sjödahl Matsson, Jack Lipton, Ulrika Nordström, Åsa Westrin, Patrik Brundin, Lena Brundin
BACKGROUND: Exendin-4 is a peptide agonist of the glucagon-like peptide-1 (GLP-1) receptor, currently in clinical trials as a potential disease-modifying therapy for Parkinson's disease. In light of this, it is important to understand potential modes of action of exendin-4 in the brain. Exendin-4 is neuroprotective and has been proposed to be directly anti-inflammatory, and that this is one way it reduces neurodegeneration. However, prior studies have focused on animal models involving both neurodegeneration and inflammation, therefore, it is also possible that the observed decreased inflammation is secondary to reduced neurodegeneration...
2017: Journal of Parkinson's Disease
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
#6
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/28340576/polysaccharides-from-ganoderma-lucidum-attenuate-microglia-mediated-neuroinflammation-and-modulate-microglial-phagocytosis-and-behavioural-response
#7
Qing Cai, Yuanyuan Li, Gang Pei
BACKGROUND: Ganoderma lucidum (GL) has been widely used in Asian countries for hundreds of years to promote health and longevity. The pharmacological functions of which had been classified, including the activation of innate immune responses, suppression of tumour and modulation of cell proliferations. Effective fractions of Ganoderma lucidum polysaccharides (GLP) had already been reported to regulate the immune system. Nevertheless, the role of GLP in the microglia-mediated neuroinflammation has not been sufficiently elucidated...
March 24, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28337257/subcutaneous-liraglutide-ameliorates-methylglyoxal-induced-alzheimer-like-tau-pathology-and-cognitive-impairment-by-modulating-tau-hyperphosphorylation-and-glycogen-synthase-kinase-3%C3%AE
#8
Liqin Qi, Zhou Chen, Yanping Wang, Xiaoying Liu, Xiaohong Liu, Linfang Ke, Zhongjie Zheng, Xiaowei Lin, Yu Zhou, Lijuan Wu, Libin Liu
Memory deterioration and synapse damage with accumulation of β-amyloid and hyperphosphorylated tau are hallmark lesions of Alzheimer's disease (AD). Methylglyoxal (MG), a key intermediate of glucose metabolism, is elevated in AD brains and modifies Aβ42, increasing misfolding and leading to the accumulation of senile plaques. Liraglutide, an analog of glucagon-like peptide-1 (GLP-1), is neurotrophic and neuroprotective. However, whether liraglutide can protect against AD-like memory-related deficits and tau hyperphosphorylation caused by MG in vivo is not known...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28223210/a-novel-glp-1-gip-dual-receptor-agonist-protects-from-6-ohda-lesion-in-a-rat-model-of-parkinson-s-disease
#9
Jaishree Jalewa, Mohit Kumar Sharma, Simon Gengler, Christian Hölscher
The incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) are growth factors that have shown neuroprotective effects in animal models of Parkinson's and Alzheimer's disease. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. GLP-1 analogues are currently on the market as treatments for type II diabetes. We previously showed that the novel dual agonist (DA-JC1) was effective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD...
February 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28202578/p38%C3%AE-mitogen-activated-protein-kinase-signaling-mediates-exenatide-stimulated-microglial-%C3%AE-endorphin-expression
#10
Hai-Yun Wu, Xiao-Fang Mao, Hui Fan, Yong-Xiang Wang
Recent discoveries established that activation of glucagon-like peptide-1 receptors (GLP-1Rs) mediates neuroprotection and antinociception through microglial β-endorphin expression. This study aimed to explore the underlying signaling mechanisms of microglial β-endorphin. GLP-1Rs and β-endorphin were coexpressed in primary cultures of microglia. Treatment with the GLP-1R agonist exenatide concentration-dependently stimulated microglial expression of the β-endorphin precursor gene proopiomelanocortin (POMC) and peptides, with EC50 values of 4...
May 2017: Molecular Pharmacology
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
#11
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/28098360/morroniside-a-secoiridoid-glycoside-from-cornus-officinalis-attenuates-neuropathic-pain-by-activation-of-spinal-glucagon-like-peptide-1-receptors
#12
Meng Xu, Hai-Yun Wu, Hao Liu, Nian Gong, Yi-Rui Wang, Yong-Xiang Wang
BACKGROUND AND PURPOSE: Iridoid glycosides containing the double bond scaffold of cyclopentapyran are reversible and orthosteric agonists of glucagon-like peptide-1 (GLP-1) receptors and exert anti-nociceptive and neuroprotective actions. Morroniside, derived from the medicinal herb Cornus officinalis, is an atypical secoiridoid containing a six-membered cyclic inner ether fragment. Here we investigated whether morroniside was an orthosteric GLP-1 receptor agonist and had anti-hypersensitivity activities in a model of neuropathic pain...
April 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28062257/liraglutide-prevents-cognitive-decline-in-a-rat-model-of-streptozotocin-induced-diabetes-independently-from-its-peripheral-metabolic-effects
#13
Caterina Palleria, Antonio Leo, Francesco Andreozzi, Rita Citraro, Michelangelo Iannone, Rosangela Spiga, Giorgio Sesti, Andrew Constanti, Giovambattista De Sarro, Franco Arturi, Emilio Russo
Diabetes has been identified as a risk factor for cognitive dysfunctions. Glucagone like peptide 1 (GLP-1) receptor agonists have neuroprotective effects in preclinical animal models. We evaluated the effects of GLP-1 receptor agonist, liraglutide (LIR), on cognitive decline associated with diabetes. Furthermore, we studied LIR effects against hippocampal neurodegeneration induced by streptozotocin (STZ), a well-validated animal model of diabetes and neurodegeneration associated with cognitive decline. Diabetes and/or cognitive decline were induced in Wistar rats by intraperitoneal or intracerebroventricular injection of STZ and then rats were treated with LIR (300μg/kg daily subcutaneously) for 6 weeks...
March 15, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28040864/glp-1-receptor-independent-pathways-emerging-beneficial-effects-of-glp-1-breakdown-products
#14
REVIEW
Valeria Guglielmi, Paolo Sbraccia
The glucagon-like peptide-1 (GLP-1) axis has emerged as a major therapeutic target for the treatment of type 2 diabetes and, recently, of obesity. The insulinotropic activity of the native incretin hormone GLP-1(7-36)amide, which is mainly exerted through a unique G protein-coupled receptor (GLP-1R), is terminated via enzymatic cleavage by dipeptidyl peptidase-IV that generates a C-terminal GLP-1 metabolite GLP-1(9-36)amide, the major circulating form in plasma. GLP-1(28-36)amide and GLP-1(32-36)amide are further cleavage products derived from GLP-1(7-36)amide and GLP-1(9-36)amide by the action of a neutral endopeptidase known as neprilysin...
December 31, 2016: Eating and Weight Disorders: EWD
https://www.readbyqxmd.com/read/27990119/oral-administration-of-sitagliptin-activates-creb-and-is-neuroprotective-in-murine-model-of-brain-trauma
#15
Brian DellaValle, Gitte S Brix, Birgitte Brock, Michael Gejl, Jørgen Rungby, Agnete Larsen
Introduction: Traumatic brain injury is a major cause of mortality and morbidity. We have previously shown that the injectable glucagon-like peptide-1 (GLP-1) analog, liraglutide, significantly improved the outcome in mice after severe traumatic brain injury (TBI). In this study we are interested in the effects of oral treatment of a different class of GLP-1 based therapy, dipeptidyl peptidase IV (DPP-IV) inhibition on mice after TBI. DPP-IV inhibitors reduce the degradation of endogenous GLP-1 and extend circulation of this protective peptide in the bloodstream...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27942008/the-dpp4-inhibitor-linagliptin-protects-from-experimental-diabetic-retinopathy
#16
Nadine Dietrich, Matthias Kolibabka, Stephanie Busch, Petra Bugert, Ulrike Kaiser, Jihong Lin, Thomas Fleming, Michael Morcos, Thomas Klein, Andrea Schlotterer, Hans-Peter Hammes
BACKGROUND/AIMS: Dipeptidyl peptidase 4 (DPP4) inhibitors improve glycemic control in type 2 diabetes, however, their influence on the retinal neurovascular unit remains unclear. METHODS: Vasculo- and neuroprotective effects were assessed in experimental diabetic retinopathy and high glucose-cultivated C. elegans, respectively. In STZ-diabetic Wistar rats (diabetes duration of 24 weeks), DPP4 activity (fluorometric assay), GLP-1 (ELISA), methylglyoxal (LC-MS/MS), acellular capillaries and pericytes (quantitative retinal morphometry), SDF-1a and heme oxygenase-1 (ELISA), HMGB-1, Iba1 and Thy1...
2016: PloS One
https://www.readbyqxmd.com/read/27917122/glucagon-like-peptide-1-analog-liraglutide-delays-onset-of-experimental-autoimmune-encephalitis-in-lewis-rats
#17
Brian DellaValle, Gitte S Brix, Birgitte Brock, Michael Gejl, Anne M Landau, Arne Møller, Jørgen Rungby, Agnete Larsen
Introduction: Recent findings indicate that metabolic disturbances are involved in multiple sclerosis (MS) pathology and influence the susceptibility to treatment, directing attention toward anti-diabetic drugs such as metformin and pioglitazone. Liraglutide, a drug of the glucagon-like peptide-1 (GLP-1) family, is also anti-diabetic and weight-reducing and is, moreover, directly neuroprotective and anti-inflammatory in a broad spectrum of experimental models of brain disease. In this study we investigate the potential for this FDA-approved drug, liraglutide, as a treatment for MS by utilizing the experimental model, experimental autoimmune encephalitis (EAE)...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27871675/glucagon-like-peptide-1-and-the-central-peripheral-nervous-system-crosstalk-in-diabetes
#18
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
#19
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/27776993/lixisenatide-attenuates-the-detrimental-effects-of-amyloid-%C3%AE-protein-on-spatial-working-memory-and-hippocampal-neurons-in-rats
#20
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
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