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Glp-1 brain

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https://www.readbyqxmd.com/read/28430981/central-nervous-system-glp-1-receptors-regulate-islet-hormone-secretion-and-glucose-homeostasis-in-male-rats
#1
Lene Jessen, Eric P Smith, Yvonne Ulrich-Lai, James P Herman, Randy J Seeley, Darleen Sandoval, David D'Alessio
The glucagon-like peptide 1 (GLP-1) system plays an important role in blood glucose regulation, in great part through coordinate control of insulin and glucagon secretion. These effects are generally attributed to GLP-1 produced in peripheral sites, principally the intestine. GLP-1 is also produced in hindbrain neurons that signal through GLP-1 receptors (GLP-1r) expressed in brain regions involved in metabolic regulation. GLP-1 in the central nervous system (CNS) induces satiety, visceral illness, and stress responses...
April 18, 2017: Endocrinology
https://www.readbyqxmd.com/read/28416568/pharmacological-and-toxicological-properties-of-the-potent-oral-%C3%AE-secretase-modulator-bpn-15606
#2
Steven L Wagner, Kevin D Rynearson, Steven K Duddy, Can Zhang, Phuong D Nguyen, Ann Becker, Uyen Vo, Deborah Masliah, Louise Monte, Justin B Klee, Corinne M Echmalian, Weiming Xia, Luisa Quinti, Graham Johnson, Jiunn H Lin, Doo Y Kim, William C Mobley, Robert A Rissman, Rudolph E Tanzi
Alzheimer's disease is characterized neuropathologically by an abundance of 1) neuritic plaques, which are primarily composed of a fibrillar 42 amino acid amyloid β peptide, as well as 2) neurofibrillary tangles composed of aggregates of hyperphosporylated tau. Elevations in the concentrations of the Aβ42 peptide in the brain, as a result of either increased production or decreased clearance are postulated to initiate and drive the AD pathological process. We initially introduced a novel class of bridged aromatics referred to as γ-secretase modulators that inhibited the production of the Aβ42 peptide and to a lesser degree the Aβ40 peptide while concomitantly increasing the production of the carboxyl-truncated Aβ38 and Aβ37 peptides...
April 17, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28408435/neurturin-and-a-glp-1-analogue-act-synergistically-to-alleviate-diabetes-in-zucker-diabetic-fatty-rats
#3
James L Trevaskis, Chester Bittencourt Sacramento, Hani Jouihan, Safina Ali, John Le Lay, Stephanie Oldham, Nicholas Bhagroo, Brandon B Boland, Jennifer Cann, Yuan Chang, Terrence O'Day, Victor Howard, Christina Reers, Maria Sorhede Winzell, David M Smith, Michael Feigh, Pernille Barkholt, Kay Schreiter, Matthias Austen, Uwe Andag, Simon Thompson, Lutz Jermutus, Matthew P Coghlan, Joseph Grimsby, Cord Dohrmann, Christopher J Rhodes, Cristina M Rondinone, Arun Sharma
Neurturin (NRTN), a member of the glial-derived neurotrophic factor (GDNF) family, was identified from an embryonic chicken pancreatic cDNA library in a screen for secreted factors. Here, we assessed the potential antidiabetic activities of NRTN relative to liraglutide, a GLP-1 receptor agonist, in Zucker diabetic fatty (ZDF) rats. Subcutaneous administration of NRTN to 8-week-old male ZDF rats prevented the development of hyperglycemia and improved metabolic parameters similar to liraglutide. NRTN treatment increased pancreatic insulin content and β-cell mass, and prevented deterioration of islet organization...
April 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28387682/exendin-4-treatment-improves-lps-induced-depressive-like-behavior-without-affecting-pro-inflammatory-cytokines
#4
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...
April 4, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28386912/neuropsychiatric-safety-with-liraglutide-3-0%C3%A2-mg-for-weight-management-results-from-randomized-controlled-phase-2-and-3a-trials
#5
P M O'Neil, V R Aroda, A Astrup, R Kushner, D C W Lau, T A Wadden, J Brett, A Cancino, J P H Wilding
AIMS: Liraglutide, a GLP-1 receptor agonist, regulates appetite via receptors in the brain. Due to concerns over the potential of centrally-acting anti-obesity medications to affect mental health, pooled neuropsychiatric safety data from all phase 2 and 3a randomized, double-blind trials with liraglutide 3.0 mg were evaluated post hoc. METHODS: Data from the liraglutide weight-management programme were pooled. Across trials, individuals with a body mass index ≥30 kg/m(2) or ≥27 kg/m(2) with weight-related comorbidities were randomized to once-daily subcutaneous liraglutide 3...
April 6, 2017: Diabetes, Obesity & Metabolism
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...
March 23, 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/28336086/incretin-hormones-regulate-microglia-oxidative-stress-survival-and-expression-of-trophic-factors
#9
Lindsay Joy Spielman, Deanna Lynn Gibson, Andis Klegeris
The incretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) are primarily known for their metabolic function in the periphery. GLP-1 and GIP are secreted by intestinal endocrine cells in response to ingested nutrients. Both GLP-1 and GIP stimulate the production and release of insulin from pancreatic β cells as well as exhibit several growth-regulating effects on peripheral tissues. GLP-1 and GIP are also present in the brain, where they provide modulatory and anti-apoptotic signals to neurons...
March 8, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28315374/glp-1-analogue-cjc-1131-prevents-amyloid-%C3%AE-protein-induced-impirments-of-spatial-memory-and-synaptic-plasticity-in-rats
#10
Sheng-Xiao Zhang, Hong-Yan Cai, Xiao-Wen Ma, Li Yuan, Jun Zhang, Zhao-Jun Wang, Yu-Feng Li, Jin-Shun Qi
Although amyloid β protein (Aβ) has been recognized as one of the main pathological characteristics in the brain of Alzheimer's disease (AD), the effective strategies against Aβ neurotoxicity are still deficient up to now. Glucagon-like peptide 1 (GLP-1), a natural gut hormone, was found to be effective in modulating insulin signaling and neural protection, but short half-life limited its clinical application in AD treatment. CJC-1131, a newly designed GLP-1 analogue with very longer half-life, has shown good effectiveness in the treatment of type 2 diabetes mellitus (T2DM)...
March 15, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28277117/structural-imaging-of-the-brain-reveals-decreased-total-brain-and-total-gray-matter-volumes-in-obese-but-not-in-lean-women-with-polycystic-ovary-syndrome-compared-to-body-mass-index-matched-counterparts
#11
Basak Ozgen Saydam, Arzu Ceylan Has, Gurkan Bozdag, Kader Karli Oguz, Bulent Okan Yildiz
PURPOSE: To detect differences in global brain volumes and identify relations between brain volume and appetite-related hormones in women with polycystic ovary syndrome (PCOS) compared to body mass index-matched controls. METHODS: Forty subjects participated in this study. Cranial magnetic resonance imaging and measurements of fasting ghrelin, leptin and glucagon-like peptide 1 (GLP-1), as well as GLP-1 levels during mixed-meal tolerance test (MTT), were performed...
March 1, 2017: Gynecological Endocrinology
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
#12
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/28218623/dreadding-proglucagon-neurons-a-fresh-look-at-metabolic-regulation-by-the-brain
#13
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...
March 1, 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
#14
Mariana P Monteiro, Rachel L Batterham
The gastrointestinal 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 gastrointestinal tract and evidence for their role in controlling feeding behavior. Mechanistic studies that have utilized pharmacologic and/or transgenic approaches targeting an individual hormone/mediator have yielded somewhat disappointing body weight changes, often leading to the hormone/mediator in question being dismissed as a potential obesity therapy...
February 11, 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
#15
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
#16
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...
May 1, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28109096/-vildagliptin-suppresses-temporal-lobe-epilepsy-by-up-regulating-glucagon-like-peptide-1
#17
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
#18
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-analogs-act-in-the-dorsal-raphe-and-modulate-central-serotonin-to-reduce-appetite-and-body-weight
#19
Rozita H Anderberg, Jennifer E Richard, Kim Eerola, Lorena López-Ferreras, Elin Banke, Caroline Hansson, Hans Nissbrandt, Filip Berqquist, Fiona M Gribble, Frank Reimann, Ingrid Wernstedt Asterholm, Christophe M 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 antiobesity 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 central nervous system. Serotonin depletion impaired the ability of exendin-4, a clinically used GLP-1 analog, to reduce body weight in rats, suggesting that serotonin is a critical mediator of the energy balance impact of GLP-1 receptor (GLP-1R) activation...
April 2017: Diabetes
https://www.readbyqxmd.com/read/28055028/the-role-of-gut-brain-axis-in-regulating-glucose-metabolism-after-acute-pancreatitis
#20
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
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