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Glp-1 brain

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https://www.readbyqxmd.com/read/29331730/exenatide-exerts-cognitive-effects-by-modulating-the-bdnf-trkb-neurotrophic-axis-in-adult-mice
#1
Manuela Bomba, Alberto Granzotto, Vanessa Castelli, Noemi Massetti, Elena Silvestri, Lorella M T Canzoniero, Annamaria Cimini, Stefano L Sensi
Modulation of insulin-dependent signaling is emerging as a valuable therapeutic tool to target neurodegeneration. In the brain, the activation of insulin receptors promotes cell growth, neuronal repair, and protection. Altered brain insulin signaling participates in the cognitive decline seen in Alzheimer's disease patients and the aging brain. Glucagon-like peptide-1 (GLP-1) regulates insulin secretion and, along with GLP-1 analogues, enhances neurotrophic signaling and counteracts cognitive deficits in preclinical models of neurodegeneration...
December 19, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29329976/therapeutic-potential-of-spinal-glp-1-receptor-signaling
#2
REVIEW
Dongao Zhang, Gang Lv
GLP-1 signaling pathway has been well studied for its role in regulating glucose homeostasis, as well as its beneficial effects in energy and nutrient metabolism. A number of drugs based on GLP-1 have been used to treat type 2 diabetes mellitus. GLP-1R is expressed in multiple organs and numerous experimental studies have demonstrated that GLP-1 signaling pathway exhibits pro-survival functions in various disorders. In the central nervous system, stimulation of GLP-1R produces neuroprotective effects in specific neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease...
January 9, 2018: Peptides
https://www.readbyqxmd.com/read/29327400/a-vitamin-b12-conjugate-of-exendin-4-improves-glucose-tolerance-without-associated-nausea-or-hypophagia-in-rodents
#3
Elizabeth G Mietlicki-Baase, Claudia G Liberini, Jayme L Workinger, Ron L Bonaccorso, Tito Borner, David J Reiner, Kieran Koch-Laskowski, Lauren E McGrath, Rinzin Lhamo, Lauren M Stein, Bart C De Jonghe, George G Holz, Christian L Roth, Robert P Doyle, Matthew R Hayes
AIMS: While pharmacological glucagon-like peptide-1 receptor (GLP-1R) agonists are FDA-approved for treating type 2 diabetes mellitus (T2DM) and obesity, a major side effect is nausea/malaise. We recently developed a conjugate of vitamin B12 bound to the GLP-1R agonist exendin-4 (Ex4), which displays enhanced proteolytic stability and retention of GLP-1R agonism. Here, we evaluate whether the conjugate (B12-Ex4) can improve glucose tolerance without producing anorexia and malaise. MATERIALS AND METHODS: We evaluated the effects of systemic B12-Ex4 and unconjugated Ex4 on food intake and body weight change, oral glucose tolerance, and nausea/malaise in male rats, and on intraperitoneal glucose tolerance in mice...
January 12, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29316242/sustained-high-fat-diet-modulates-inflammation-insulin-signalling-and-cognition-in-mice-and-a-modified-xenin-peptide-ameliorates-neuropathology-in-a-chronic-high-fat-model
#4
Paul Denver, Victor A Gault, Paula L McClean
AIMS: Metabolic disease increases risk of Alzheimer's disease and cognitive dysfunction. Chronic high fat diet (HFD) feeding leads to cognitive impairment and neuroinflammation. This study demarcated pathological events in brain as a result of short-term to chronic HFD feeding. Efficacy of Xenin-25[Lys(13)PAL] was assessed in chronic HFD-fed mice. METHODS: C57BL/6 mice were fed HFD or normal diet for 18 days, 34 days, 10 and 21 weeks. Cognition was assessed using novel object recognition and Morris water maze...
January 5, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29274367/the-effects-of-incretin-hormones-on-cerebral-glucose-metabolism-in-health-and-disease
#5
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/29259802/the-effect-of-the-glp-1-analogue-exenatide-on-functional-connectivity-within-an-nts-based-network-in-women-with-and-without-obesity
#6
K Coveleskie, L A Kilpatrick, A Gupta, J Stains, L Connolly, J S Labus, C Sanmiguel, E A Mayer
Objective: The differential effect of GLP-1 agonist Exenatide on functional connectivity of the nucleus tractus solitaries (NTS), a key region associated with homeostasis, and on appetite-related behaviours was investigated in women with normal weight compared with women with obesity. Methods: Following an 8-h fast, 19 female subjects (11 lean, 8 obese) participated in a 2-d double blind crossover study. Subjects underwent functional magnetic resonance imaging at fast and 30-min post subcutaneous injection of 5 μg of Exenatide or placebo...
December 2017: Obesity Science & Practice
https://www.readbyqxmd.com/read/29247677/brainstem-glp-1-signalling-contributes-to-cancer-anorexia-cachexia-syndrome-in-the-rat
#7
Tito Borner, Claudia G Liberini, Thomas A Lutz, Thomas Riediger
The cancer anorexia-cachexia syndrome (CACS) is a frequent and severe condition in cancer patients. Currently, no pharmacological treatment is approved for the therapy of CACS. Centrally, glucagon-like peptide-1 (GLP-1) is expressed in the nucleus tractus solitarii (NTS) and is implicated in malaise, nausea and food aversion. The NTS is reciprocally connected to brain sites implicated in the control of energy balance including the area postrema (AP), which mediates CACS in certain tumour models. Given the role of GLP-1 as a mediator of anorexia under acute sickness conditions, we hypothesized that brainstem GLP-1 signalling might play a role in the mediation of CACS...
December 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29246184/liraglutide-modulates-gabaergic-signaling-in-rat-hippocampal-ca3-pyramidal-neurons-predominantly-by-presynaptic-mechanism
#8
Omar Babateen, Sergiy V Korol, Zhe Jin, Amol K Bhandage, Aikeremu Ahemaiti, Bryndis Birnir
BACKGROUND: γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain where it regulates activity of neuronal networks. The receptor for glucagon-like peptide-1 (GLP-1) is expressed in the hippocampus, which is the center for memory and learning. In this study we examined effects of liraglutide, a GLP-1 analog, on GABA signaling in CA3 hippocampal pyramidal neurons. METHODS: We used patch-clamp electrophysiology to record synaptic and tonic GABA-activated currents in CA3 pyramidal neurons in rat hippocampal brain slices...
December 16, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29235507/blood-brain-glucose-transfer-in-alzheimer-s-disease-effect-of-glp-1-analog-treatment
#9
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/29228720/gastric-myoelectric-activity-during-cisplatin-induced-acute-and-delayed-emesis-reveals-a-temporal-impairment-of-slow-waves-in-ferrets-effects-not-reversed-by-the-glp-1-receptor-antagonist-exendin-9-39
#10
Zengbing Lu, Man P Ngan, Ge Lin, David T W Yew, Xiaodan Fan, Paul L R Andrews, John A Rudd
Preclinical studies show that the glucagon-like peptide-1 (GLP-1) receptor antagonist, exendin (9-39), can reduce acute emesis induced by cisplatin. In the present study, we investigate the effect of exendin (9-39) (100 nmol/24 h, i.c.v), on cisplatin (5 mg/kg, i.p.)-induced acute and delayed emesis and changes indicative of 'nausea' in ferrets. Cisplatin induced 37.2 ± 2.3 and 59.0 ± 7.7 retches + vomits during the 0-24 (acute) and 24-72 h (delayed) periods, respectively. Cisplatin also increased (P<0...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29226617/activation-of-glucagon-like-peptide-1-receptors-in-the-nucleus-accumbens-attenuates-cocaine-seeking-in-rats
#11
Nicole S Hernandez, Bernadette O'Donovan, Pavel I Ortinski, Heath D Schmidt
Recent evidence indicates that activation of glucagon-like peptide-1 (GLP-1) receptors reduces cocaine-mediated behaviors and cocaine-evoked dopamine release in the nucleus accumbens (NAc). However, no studies have examined the role of NAc GLP-1 receptors in the reinstatement of cocaine-seeking behavior, an animal model of relapse. Here, we show that systemic infusion of a behaviorally relevant dose of the GLP-1 receptor agonist exendin-4 penetrated the brain and localized with neurons and astrocytes in the NAc...
December 11, 2017: Addiction Biology
https://www.readbyqxmd.com/read/29223528/glp-1-receptor-agonists-downregulate-aberrant-gnt-iii-expression-in-alzheimer-s-disease-models-through-the-akt-gsk-3%C3%AE-%C3%AE-catenin-signaling
#12
Ying Wang, Song Chen, Zheng Xu, Suting Chen, Wenbing Yao, Xiangdong Gao
Alterations of glycoprotein glycans contribute to a wide variety of diseases. Bisecting N-acetylglucosamine (GlcNAc) levels increased in the cerebrospinal fluid of most Alzheimer's disease (AD) patients, and the mRNA levels of N-acetylglucosaminyltransferase III (GnT-III), a glycosyltransferase responsible for synthesizing a bisecting GlcNAc residue, were found highly expressed in the brains of AD patients. In our previous studies, glucagon-like peptide-1 (GLP-1) and its mimetics showed neuroprotective effects...
December 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29221794/glp-1-action-in-the-mouse-bed-nucleus-of-the-stria-terminalis
#13
Diana L Williams, Nicole A Lilly, Ian J Edwards, Pallas Yao, James E Richards, Stefan Trapp
Glucagon-like peptide-1 (GLP-1) injected into the brain reduces food intake. Similarly, activation of preproglucagon (PPG) cells in the hindbrain which synthesize GLP-1, reduces food intake. However, it is far from clear whether this happens because of satiety, nausea, reduced reward, or even stress. Here we explore the role of the bed nucleus of the stria terminalis (BNST), an area involved in feeding control as well as stress responses, in GLP-1 responses. Using cre-expressing mice we visualized projections of NTS PPG neurons and GLP-1R-expressing BNST cells with AAV-driven Channelrhodopsin-YFP expression...
December 5, 2017: Neuropharmacology
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
#14
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/29175324/lixisenatide-reduces-amyloid-plaques-neurofibrillary-tangles-and-neuroinflammation-in-an-app-ps1-tau-mouse-model-of-alzheimer-s-disease
#15
Hong-Yan Cai, Jun-Ting Yang, Zhao-Jun Wang, Jun Zhang, Wei Yang, Mei-Na Wu, Jin-Shun Qi
Type 2 diabetes mellitus (T2DM) has been identified as a high risk factor for Alzheimer's disease (AD). The impairment of insulin signaling has been found in AD brain. Glucagon-like peptide-1 (GLP-1) is an incretin hormone, normalises insulin signaling and acts as a neuroprotective growth factor. We have previously shown that the long-lasting GLP-1 receptor (GLP-1R) agonist lixisenatide plays an important role in memory formation, synaptic plasticity and cell proliferation of rats. In the follow-up study, we analysed the neuroprotective effect and mechanism of lixisenatide, injected for 60 days at 10 nmol/kg i...
November 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29165354/the-role-of-glucagon-like-peptide-1-glp1-in-type-3-diabetes-glp-1-controls-insulin-resistance-neuroinflammation-and-neurogenesis-in-the-brain
#16
REVIEW
Choon Sang Bae, Juhyun Song
Alzheimer's disease (AD), characterized by the aggregation of amyloid-β (Aβ) protein and neuroinflammation, is the most common neurodegenerative disease globally. Previous studies have reported that some AD patients show impaired glucose utilization in brain, leading to cognitive decline. Recently, diabetes-induced dementia has been called "type 3 diabetes", based on features in common with those of type 2 diabetes and the progression of AD. Impaired glucose uptake and insulin resistance in the brain are important issues in type 3 diabetes, because these problems ultimately aggravate memory dysfunction in the brain...
November 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29163019/bile-acid-signaling-pathways-from-the-enterohepatic-circulation-to-the-central-nervous-system
#17
REVIEW
Kim L Mertens, Andries Kalsbeek, Maarten R Soeters, Hannah M Eggink
Bile acids are best known as detergents involved in the digestion of lipids. In addition, new data in the last decade have shown that bile acids also function as gut hormones capable of influencing metabolic processes via receptors such as FXR (farnesoid X receptor) and TGR5 (Takeda G protein-coupled receptor 5). These effects of bile acids are not restricted to the gastrointestinal tract, but can affect different tissues throughout the organism. It is still unclear whether these effects also involve signaling of bile acids to the central nervous system (CNS)...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29156855/differences-in-leptin-ghrelin-and-glucagon-like-peptide-1-levels-between-religious-fasting-and-normal-fasting
#18
Özge Telci Çaklılı, Banu İşbilen, Gülcan Yavuz, Selcan Tülü, Banu Mesçi, Aytekin Oğuz
Background/aim: Leptin, ghrelin, and glucagon-like peptide-1 (GLP-1) affect hunger, satiety feelings, and food intake. We hypothesized that during Ramadan, if the brain knows that the body will be hungry until sunset, there may be differences between leptin, ghrelin, and GLP-1 levels in Ramadan and non-Ramadan fasting. Materials and methods: This study had two phases. In the first phase, the participants were asked to skip the dawn meal of Ramadan (suhur), so that 12 h of fasting could be achieved. Participants ceased food intake at midnight, and at noon blood was drawn...
August 23, 2017: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/29144968/a-synaptic-basis-for-glp-1-action-in-the-brain
#19
Sandrine Lefort, Matthias H Tschöp, Cristina García-Cáceres
Unraveling the brain control of metabolism may generate opportunities to discover novel precision medicines for obesity and diabetes. In this issue of Neuron, Liu et al. (2017) identify a novel glucagon-like peptide (GLP)-1 receptor-dependent signaling process that exerts anorexigenic action via the regulation of AMPA receptor subunit composition in the hypothalamus.
November 15, 2017: Neuron
https://www.readbyqxmd.com/read/29129776/glucagon-like-peptide-1-glp-1-and-neurotransmitters-signaling-in-epilepsy-an-insight-review
#20
REVIEW
Prashant Koshal, Sumit Jamwal, Puneet Kumar
Epilepsy is one of the most prevalent neurological disorder affecting more than 50 million people worldwide. Numerous studies have suggested that an imbalance in glutamatergic (excitatory) and GABAergic (inhibitory) neurotransmitter system is one of the dominating pathophysiological mechanisms underlying the occurrence and progression of seizures. Further, this alteration in GABAergic and glutamatergic system disrupts the delicate balance of other neurotransmitters system in the brain. Emerging strides have documented the protective role of GLP-1 signaling on altered neurotransmitters signaling in Epilepsy and associated co-morbidities...
November 9, 2017: Neuropharmacology
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