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Glp-1 brain

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https://www.readbyqxmd.com/read/28218623/dreadding-proglucagon-neurons-a-fresh-look-at-metabolic-regulation-by-the-brain
#1
Jonathan E Campbell, David A D'Alessio
Glucagon-like peptide 1 receptor (GLP-1R) signaling in the CNS has been linked to reduced food intake, lower body weight, improved glucose homeostasis, and activation of CNS stress axes. GLP-1 is produced by cells that express proglucagon (GCG); however, the stimuli that activate GCG+ neurons are not well known, which has made understanding the role of this neuronal population in the CNS a challenge. In this issue of the JCI, Gaykema et al. use designer receptors exclusively activated by designer drugs (DREADD) technology to specifically activate GCG+ neurons in mouse models...
February 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28193513/the-importance-of-the-gastrointestinal-tract-in-controlling-food-intake-and-regulating-energy-balance
#2
M P Monteiro, R L Batterham
The gastrointestinal (GI) tract, the key interface between ingested nutrients and the body, plays a critical role in regulating energy homeostasis. Gut-derived signals convey information regarding incoming nutrients to the brain, initiating changes in eating behavior and energy expenditure, to maintain energy balance. Here we review hormonal, neural and nutrient signals emanating from the GI tract and evidence for their role in controlling feeding behavior. Mechanistic studies that have utilized pharmacological and/or transgenic approaches targeting an individual hormone/mediator have yielded somewhat disappointing bodyweight changes, often leading to the hormone/mediator in question being dismissed as a potential obesity therapy...
February 10, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28144621/glp-1r-signaling-directly-activates-arcuate-nucleus-kisspeptin-action-in-brain-slices-but-does-not-rescue-luteinizing-hormone-inhibition-in-ovariectomized-mice-during-negative-energy-balance
#3
Kristy M Heppner, Arian F Baquero, Camdin M Bennett, Sarah R Lindsley, Melissa A Kirigiti, Baylin Bennett, Martha A Bosch, Aaron J Mercer, Oline K Rønnekleiv, Cadence True, Kevin L Grove, M Susan Smith
Kisspeptin (Kiss1) neurons in the hypothalamic arcuate nucleus (ARC) are key components of the hypothalamic-pituitary-gonadal axis, as they regulate the basal pulsatile release of gonadotropin releasing hormone (GnRH). ARC Kiss1 action is dependent on energy status, and unmasking metabolic factors responsible for modulating ARC Kiss1 neurons is of great importance. One possible factor is glucagon-like peptide 1 (GLP-1), an anorexigenic neuropeptide produced by brainstem preproglucagon neurons. Because GLP fiber projections and the GLP-1 receptor (GLP-1R) are abundant in the ARC, we hypothesized that GLP-1R signaling could modulate ARC Kiss1 action...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28119159/hindbrain-dpp-iv-inhibition-improves-glycemic-control-and-promotes-negative-energy-balance
#4
Elizabeth G Mietlicki-Baase, Lauren E McGrath, Kieran Koch-Laskowski, Joanna Krawczyk, Tram Pham, Rinzin Lhamo, David J Reiner, Matthew R Hayes
The beneficial glycemic and food intake-suppressive effects of glucagon-like peptide-1 (GLP-1) have made this neuroendocrine system a leading target for pharmacological approaches to the treatment of diabetes and obesity. One strategy to increase the activity of endogenous GLP-1 is to prevent the rapid degradation of the hormone by the enzyme dipeptidyl peptidase-IV (DPP-IV). However, despite the expression of both DPP-IV and GLP-1 in the brain, and the clear importance of central GLP-1 receptor (GLP-1R) signaling for glycemic and energy balance control, the metabolic effects of central inhibition of DPP-IV activity are unclear...
January 22, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28109096/-vildagliptin-suppresses-temporal-lobe-epilepsy-by-up-regulating-glucagon-like-peptide-1
#5
Yue-Tao Wen, Kun-Lun Wu, Quan-Hong Shi
OBJECTIVE: To investigate the effect of vildagliptin on pentamethazol (PTZ)-induced epilepsy in rats and explore the molecular mechanism. METHODS: Samples of temporal cortex from 23 patients with temporal lobe epilepsy were collected as epilepsy group and samples of temporal cortex from 14 patients with brain trauma were used as control group. Ninety male SD rats were randomly divided into control group (group A), PTZ-induced epilepsy group (group B), saline 2 mL/kg group (group C), vildagliptin 2...
January 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28062257/liraglutide-prevents-cognitive-decline-in-a-rat-model-of-streptozotocin-induced-diabetes-independently-from-its-peripheral-metabolic-effects
#6
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/28057699/glucagon-like-peptide-1-and-its-analogues-act-in-the-dorsal-raphe-and-modulate-central-serotonin-to-reduce-appetite-and-body-weight
#7
Rozita H Anderberg, Jennifer E Richard, Kim Eerola, Lorena Lopez Ferreras, Elin Banke Nordbeck, Caroline Hansson, Hans Nissbrandt, Filip Berqquist, Fiona M Gribble, Frank Reimann, Ingrid Wernstedt-Asterholm, Christophe Lamy, Karolina P Skibicka
Glucagon-like peptide-1 (GLP-1) and serotonin play critical roles in energy balance regulation. Both systems are exploited clinically as anti-obesity strategies. Surprisingly whether they interact in order to regulate energy balance is poorly understood. Here we investigated mechanisms by which GLP-1 and serotonin interact at the level of the CNS. Serotonin depletion impaired the ability of exendin-4, a clinically utilized GLP-1 analogue, to reduce body weight in rats, suggesting serotonin is a critical mediator of the energy balance impact of GLP-1R activation...
January 5, 2017: Diabetes
https://www.readbyqxmd.com/read/28055028/the-role-of-gut-brain-axis-in-regulating-glucose-metabolism-after-acute-pancreatitis
#8
Sayali A Pendharkar, Varsha M Asrani, Rinki Murphy, Richard Cutfield, John A Windsor, Maxim S Petrov
OBJECTIVES: Diabetes has become an epidemic in developed and developing countries alike, with an increased demand for new efficacious treatments. A large body of pre-clinical evidence suggests that the gut-brain axis may be exploited as a potential therapeutic target for defective glucose homeostasis. This clinical study aimed to investigate a comprehensive panel of glucoregulatory peptides, released by both the gut and brain, in individuals after acute pancreatitis. METHODS: Fasting levels of glucagon-like peptide-1 (GLP-1), glicentin, oxyntomodulin, peptide YY, ghrelin, cholecystokinin, vasoactive intestinal peptide (VIP), and secretin were studied...
January 5, 2017: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/27994501/blockade-of-central-glp-1-receptors-deteriorates-the-improvement-of-diabetes-after-ileal-transposition
#9
Weijie Chen, Qianqian Xu, Yiding Xiao, Jiaolin Zhou, Weimin Zhang, Guole Lin, Fengying Gong
Background: The mechanism of improvement of type 2 diabetes mellitus induced by ileal transposition (IT) is undefined. Our aim was to investigate the possible role of central glucagon-like peptide 1 (GLP-1) after IT. Methods: Ninety male diabetic rats were randomly divided into the IT, sham IT (S-IT) and control group. The food intake, glucose metabolism and GLP-1 level were measured. Subsequently, we administered GLP-1 antagonist via lateral brain ventricle cannula to block central GLP-1 receptor, and verified whether the food intake, glucose metabolism changed...
2016: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/27990119/oral-administration-of-sitagliptin-activates-creb-and-is-neuroprotective-in-murine-model-of-brain-trauma
#10
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/27966074/brain-defective-insulin-signaling-is-associated-to-late-cognitive-impairment-in-post-septic-mice
#11
Fernanda S Neves, Patrícia T Marques, Fernanda Barros-Aragão, José Bruno Nunes, Aline M Venancio, Danielle Cozachenco, Rudimar L Frozza, Giselle F Passos, Robson Costa, Jade de Oliveira, Daiane F Engel, Andreza F De Bem, Claudia F Benjamim, Fernanda G De Felice, Sergio T Ferreira, Julia R Clarke, Claudia P Figueiredo
Sepsis survivors frequently develop late cognitive impairment. Because little is known on the mechanisms of post-septic memory deficits, there are no current effective approaches to prevent or treat such symptoms. Here, we subjected mice to severe sepsis induced by cecal ligation and puncture (CLP) and evaluated the sepsis-surviving animals in the open field, novel object recognition (NOR), and step-down inhibitory avoidance (IA) task at different times after surgery. Post-septic mice (30 days post-surgery) failed in the NOR and IA tests but exhibited normal performance when re-evaluated 45 days after surgery...
December 13, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27917122/glucagon-like-peptide-1-analog-liraglutide-delays-onset-of-experimental-autoimmune-encephalitis-in-lewis-rats
#12
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/27915035/hyperinsulinaemic-hypoglycaemia-in-children-and-adults
#13
REVIEW
Pratik Shah, Sofia A Rahman, Huseyin Demirbilek, Maria Güemes, Khalid Hussain
Pancreatic β cells are functionally programmed to release insulin in response to changes in plasma glucose concentration. Insulin secretion is precisely regulated so that, under normal physiological conditions, fasting plasma glucose concentrations are kept within a narrow range of 3·5-5·5 mmol/L. In hyperinsulinaemic hypoglycaemia, insulin secretion becomes dysregulated (ie, uncoupled from glucose metabolism) so that insulin secretion persists in the presence of low plasma glucose concentrations. Hyperinsulinaemic hypoglycaemia is the most common cause of severe and persistent hypoglycaemia in neonates and children...
November 30, 2016: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/27856285/neurotrophic-and-neuroprotective-effects-of-oxyntomodulin-in-neuronal-cells-and-a-rat-model-of-stroke
#14
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/27782127/endogenous-glucagon-like-peptide-1-receptor-signaling-in-the-nucleus-tractus-solitarius-is-required-for-food-intake-control
#15
Amber L Alhadeff, Blake D Mergler, Derek J Zimmer, Christopher A Turner, David J Reiner, Heath D Schmidt, Harvey J Grill, Matthew R Hayes
Alhough the glucagon-like peptide-1 (GLP-1) system is critical to energy balance control and is a target for obesity pharmacotherapies, the receptor-population-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. As 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...
December 21, 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
#16
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)...
December 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
#17
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
#18
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-mechanistic-and-clinical-relevance
#19
Gemma Pujadas, Daniel J Drucker
Regulatory peptides produced in islet and gut endocrine cells, including glucagon, glucagon-like peptide-1 (GLP-1), GLP-2, and glucose-dependent insulinotropic polypeptide, exert actions with considerable metabolic importance and translational relevance. Although the clinical development of GLP-1 receptor agonists and dipeptidyl peptidase-4 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...
December 2016: Endocrine Reviews
https://www.readbyqxmd.com/read/27722184/the-physiological-role-of-the-brain-glp-1-system-in-stress
#20
REVIEW
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
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