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Glp-1 brain

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https://www.readbyqxmd.com/read/29790260/endogenous-glp-1-alters-postprandial-functional-connectivity-between-homeostatic-and-reward-related-brain-regions-involved-in-the-regulation-of-appetite-in-healthy-lean-males-a-pilot-study
#1
Anne Christin Meyer-Gerspach, Huynh Giao Ly, Stefan Borgwardt, Patrick Dupont, Christoph Beglinger, Lukas Van Oudenhove, Bettina K Wölnerhanssen
AIMS: Peripheral infusion of glucagon-like peptide-1 (GLP-1) can affect brain activity in areas involved in the regulation of appetite, including hypothalamic and reward-related brain regions. In contrast, the physiological role of endogenous GLP-1 in the central regulation of appetite has hardly been investigated. MATERIALS AND METHODS: The study was performed as randomized, cross-over trial. Twelve healthy volunteers received an intragastric (ig) glucose (gluc) load with or without intravenous (iv) exendin9-39 (ex9-39; specific GLP-1 receptor antagonist)...
May 22, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29776406/the-effect-of-dpp-4-inhibition-to-improve-functional-outcome-after-stroke-is-mediated-by-the-sdf-1%C3%AE-cxcr4-pathway
#2
Fausto Chiazza, Harald Tammen, Hiranya Pintana, Grazyna Lietzau, Massimo Collino, Thomas Nyström, Thomas Klein, Vladimer Darsalia, Cesare Patrone
BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are approved drugs for the treatment of hyperglycemia in patients with type 2 diabetes. These effects are mainly mediated by inhibiting endogenous glucagon-like peptide-1 (GLP-1) cleavage. Interestingly, gliptins can also improve stroke outcome in rodents independently from GLP1. However, the underlying mechanisms are unknown. Stromal cell-derived factor-1α (SDF-1α) is a DPP-4 substrate and CXCR4 agonist promoting beneficial effects in injured brains...
May 19, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29735436/-nicorandil-improves-cognitive-dysfunction-in-mice-with-streptozotocin-induced-diabetes
#3
Wen-Hui Yan, Chun-Xi Zhang, Tong Xing, Xue Gong, Yu-Xuan Yang, Yi-Nuo Li, Xuan Liu, Jiamaliding Ayijiang, Ye Yu, Meng Zhang, Li-Na Chen
OBJECTIVE: To observe the protective effects of potassium channel opener nicorandil against cognitive dysfunction in mice with streptozotocin (STZ)-induced diabetes. METHODS: C57BL/6J mouse models of type 1 diabetes mellitus (T1DM) were established by intraperitoneal injection of STZ and received daily treatment with intragastric administration of nicorandil or saline (model group) for 4 consecutive weeks, with normal C57BL/6J mice serving as control. Fasting blood glucose level was recorded every week and Morris water maze was used to evaluate the cognitive behavior of the mice in the 4th week...
April 20, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/29697857/the-protective-effects-of-melatonin-and-glucagon-like-peptide-1-receptor-agonist-liraglutide-on-gastric-ischemia-reperfusion-injury-in-high-fat-sucrose-fed-rats
#4
Hanan A Mubarak, Manal M Mahmoud, Heba S Shoukry, Dina H Merzeban, Safinaz S Sayed, Laila A Rashed
Ischemia-reperfusion (I-R) injury is a serious pathology that is often encountered with thrombotic events, during surgery when blood vessels are cross-clamped, and in organs for transplantation. Increased oxidative stress is the main pathology in I-R injury, as assessed in studies on the heart, kidney, and brain with little data available on gastric I-R (GI-R). Liraglutide is a GLP-1receptor agonist that has insulinotropic and weight reducing actions, and melatonin that has much studied as a chronotropic hormone; have also studied as being antioxidative stress agents...
April 26, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29671019/lixisenatide-a-novel-glp-1-analog-protects-against-cerebral-ischemia-reperfusion-injury-in-diabetic-rats
#5
Rania G Abdel-Latif, Gehan H Heeba, Ashraf Taye, Mohamed M A Khalifa
Type 2 diabetes mellitus (T2DM) is a major risk factor for ischemic stroke accompanied by vascular dysfunction and poor cerebrovascular outcome. Lixisenatide is a glucagon like peptide-1 (GLP-1) analog that is recently used for T2DM treatment with established neuroprotective properties. This study investigated and compared the neuroprotective effect of lixisenatide against glimepiride on diabetic rats subjected to global cerebral ischemia/reperfusion (I/R) injury. T2DM-induced adult male Wistar rats were administered lixisenatide or glimepiride prior to induction of global cerebral I/R-induced injury...
April 18, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29667232/the-pleiotropic-cardiovascular-effects-of-dipeptidyl-peptidase-4-inhibitors
#6
REVIEW
Angelo Avogaro, Gian Paolo Fadini
Patients with Type 2 Diabetes have an excess risk for cardiovascular disease. One of the several approaches, included in the Guidelines for the management of Type 2 Diabetes, is based on dipeptidyl peptidase 4 (DPP-4; also termed CD26) inhibitors (DPP-4-I), also called gliptins. Gliptins inhibit the degradation of glucagon-like peptide-1 GLP-1RA: this effect is associated with increased circulating insulin-to-glucagon ratio, and a consequent reduction of HbA1c. Beside incretin hormones, there are several proteins that may be affected by DPP-4 and its inhibition: among these some are relevant for the cardiovascular system homeostasis such as SDF-1α and its receptor CXCR4, brain natriuretic peptides, neuropeptide Y, and peptide YY...
April 17, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29604345/inflammation-insulin-signaling-and-cognitive-function-in-aged-app-ps1-mice
#7
Paul Denver, Andrew English, Paula L McClean
Cognitive dysfunction and neuroinflammation are typical in Alzheimer's disease (AD), but are also associated with normal aging, albeit less severely. Insulin resistance in the brain has been demonstrated in AD patients and is thought to be involved in AD pathophysiology. Using 15-18 month-old APP/PS1 mice, this study measured peripheral and central insulin signaling and sensitivity, inflammatory markers in brain and plasma and oxidative stress and synapse density in the brain. Novel object recognition, Morris water maze and reversal water maze tasks were performed to assess cognitive function in aged APP/PS1 mice and wild type littermates...
March 29, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29603541/augmentation-of-glucagon-like-peptide-1-receptor-signalling-by-neprilysin-inhibition-potential-implications-for-patients-with-heart-failure
#8
REVIEW
Milton Packer
Augmentation of glucagon-like peptide-1 (GLP-1) receptor signalling is an established approach to the treatment of type 2 diabetes. However, endogenous GLP-1 and long-acting GLP-1 receptor analogues are degraded not only by dipeptidyl peptidase-4, but also by neprilysin. This observation raises the possibilities that endogenous GLP-1 contributes to the clinical effects of neprilysin inhibition and that patients concurrently treated with sacubitril/valsartan and incretin-based drugs may experience important drug-drug interactions...
March 30, 2018: European Journal of Heart Failure
https://www.readbyqxmd.com/read/29601817/glp-1-receptor-agonist-liraglutide-exerts-central-action-to-induce-%C3%AE-cell-proliferation-through-medulla-to-vagal-pathway-in-mice
#9
Parmila Kumari, Masanori Nakata, Bo Yang Zhang, Zesemdorj Otgon-Uul, Toshihiko Yada
Endogenous GLP-1 and GLP-1 receptor agonists (GLP-1RAs) regulate glucose metabolism via common and distinct mechanisms. Postprandial release of GLP-1 is modest and it is degraded by DPP-4 within 2 min, and hence it cannot enter the brain in substantial amount. In contrast, DPP-4-resistant GLP-1RAs are administered at 10 times higher concentration than endogenous GLP-1 level, which enables them to reach several brain regions including ARC and AP, the areas implicated in glucose metabolism. Hence, some of the effects of GLP-1RAs observed clinically and experimentally, including pancreatic β-cell proliferation, are thought to involve the brain...
March 27, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29549796/post-treatment-with-the-glp-1-analogue-liraglutide-alleviate-chronic-inflammation-and-mitochondrial-stress-induced-by-status-epilepticus
#10
Rui-Fang Wang, Guo-Fang Xue, Christian Hölscher, Miao-Jing Tian, Peng Feng, Ji-Ying Zheng, Dong-Fang Li
Glucagon-like peptide-1(GLP-1) is a growth factor that has neuroprotective and anti-inflammatory properties. The protease resistant GLP-1 analogue liraglutide has been shown to be neuroprotective in previous studies in animal models of Alzheimer's disease or Parkinson's disease. Status epilepticus (SE) is a complex disorder, involving many underlying pathological processes, including excitotoxic and chronic inflammatory events. The present pilot study aims to investigate whether liraglutide alleviates the chronic inflammation response and mitochondrial stress induced by SE in the lithium-pilocarpine animal model...
May 2018: Epilepsy Research
https://www.readbyqxmd.com/read/29546316/cd36-modulates-fasting-and-preabsorptive-hormone-and-bile-acid-levels
#11
Cyndya A Shibao, Jorge E Celedonio, Robyn Tamboli, Reem Sidani, Latisha Love-Gregory, Terri Pietka, Yanhua Xiong, Yan Wei, Naji N Abumrad, Nada A Abumrad, Charles Robb Flynn
Context: Abnormal fatty acid (FA) metabolism contributes to diabetes and cardiovascular disease. The FA receptor CD36 has been linked to risk of metabolic syndrome. In rodents CD36 regulates various aspects of fat metabolism, but whether it has similar actions in humans is unknown. We examined the impact of a coding single-nucleotide polymorphism in CD36 on postprandial hormone and bile acid (BA) responses. Objective: To examine whether the minor allele (G) of coding CD36 variant rs3211938 (G/T), which reduces CD36 level by ∼50%, influences hormonal responses to a high-fat meal (HFM)...
May 1, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29510158/endogenous-glp-1-in-lateral-septum-contributes-to-stress-induced-hypophagia
#12
Sarah J Terrill, Calyn B Maske, Diana L Williams
Glucagon-like peptide 1 (GLP-1) neurons of the caudal brainstem project to many brain areas, including the lateral septum (LS), which has a known role in stress responses. Previously, we showed that endogenous GLP-1 in the LS plays a physiologic role in the control of feeding under non-stressed conditions, however, central GLP-1 is also involved in behavioral and endocrine responses to stress. Here, we asked whether LS GLP-1 receptors (GLP-1R) contribute to stress-induced hypophagia. Male rats were implanted with bilateral cannulas targeting the dorsal subregion of the LS (dLS)...
March 3, 2018: Physiology & Behavior
https://www.readbyqxmd.com/read/29501615/glucagon-like-peptide-1-mediates-effects-of-oral-galactose-in-streptozotocin-induced-rat-model-of-sporadic-alzheimer-s-disease
#13
Ana Knezovic, Jelena Osmanovic Barilar, Ana Babic, Robert Bagaric, Vladimir Farkas, Peter Riederer, Melita Salkovic-Petrisic
Insulin resistance and metabolic dysfunction in the brain are considered to be the pathophysiological core of sporadic Alzheimer's disease (sAD). In line with that fact, nutrients that could have therapeutic effects at this level have been investigated as possible targets in AD therapy. Galactose, an epimer of glucose, may serve as an alternative source of energy, and given orally may stimulate secretion of the incretin hormone glucagon-like peptide-1 (GLP-1). Our preliminary research indicated that oral galactose might prevent development of memory impairment in a rat model of sAD generated by intracerebroventricular administration of streptozotocin (STZ-icv)...
February 28, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29497166/glucagon-like-peptide-1-receptor-activation-in-the-ventral-tegmental-area-attenuates-cocaine-seeking-in-rats
#14
Nicole S Hernandez, Kelsey Y Ige, Elizabeth G Mietlicki-Baase, Gian Carlo Molina-Castro, Christopher A Turner, Matthew R Hayes, Heath D Schmidt
Novel molecular targets are needed to develop new medications for the treatment of cocaine addiction. Here we investigated a role for glucagon-like peptide-1 (GLP-1) receptors in the reinstatement of cocaine-seeking behavior, an animal model of relapse. We showed that peripheral administration of the GLP-1 receptor agonist exendin-4 dose dependently reduced cocaine seeking in rats at doses that did not affect ad libitum food intake, meal patterns or body weight. We also demonstrated that systemic exendin-4 penetrated the brain where it putatively bound receptors on both neurons and astrocytes in the ventral tegmental area (VTA)...
February 14, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29484303/liraglutide-a-glp-1-receptor-agonist-which-decreases-hypothalamic-5-ht2a-receptor-expression-reduces-appetite-and-body-weight-independently-of-serotonin-synthesis-in-mice
#15
Katsunori Nonogaki, Takao Kaji
A recent report suggested that brain-derived serotonin (5-HT) is critical for maintaining weight loss induced by glucagon-like peptide-1 (GLP-1) receptor activation in rats and that 5-HT2A receptors mediate the feeding suppression and weight loss induced by GLP-1 receptor activation. Here, we show that changes in daily food intake and body weight induced by intraperitoneal administration of liraglutide, a GLP-1 receptor agonist, over 4 days did not differ between mice treated with the tryptophan hydroxylase (Tph) inhibitor p-chlorophenylalanine (PCPA) for 3 days and mice without PCPA treatment...
2018: Journal of Diabetes Research
https://www.readbyqxmd.com/read/29473944/non-endocannabinoid-n-acylethanolamines-and-2-monoacylglycerols-in-the-intestine
#16
REVIEW
Harald S Hansen, Vasiliki Vana
This review focuses on recent findings of the physiological and pharmacological role of non-endocannabinoid N-acylethanolamines (NAEs) and 2-monoacylglycerols (2-MAGs) in the intestine and their involvement in the gut-brain signalling. Dietary fat suppresses food intake, and much research concerns the known gut peptides, for example, glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK). NAEs and 2-MAGs represent another class of local gut signals most probably involved in the regulation of food intake...
February 23, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29462693/two-novel-dual-glp-1-gip-receptor-agonists-are-neuroprotective-in-the-mptp-mouse-model-of-parkinson-s-disease
#17
Peng Feng, Xiangjian Zhang, Dongfang Li, Chenhui Ji, Ziyue Yuan, Ruifang Wang, Guofang Xue, Guanglai Li, Christian Hölscher
Type 2 diabetes mellitus (T2DM) is a risk factors for developing Parkinson's disease (PD). Insulin desensitization is observed in the brains of PD patients, which may be an underlying mechanism that promotes neurodegeneration. Incretin hormones are growth factors that can re-sensitize insulin signalling. We have previously shown that analogues of the incretins GLP-1 or GIP have neuroprotective effects in the MPTP mouse model of PD. Novel dual GLP-1/GIP receptor agonists have been developed as treatments for T2DM...
May 1, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29435980/the-diabetes-drug-liraglutide-reverses-cognitive-impairment-in-mice-and-attenuates-insulin-receptor-and-synaptic-pathology-in-a-non-human-primate-model-of-alzheimer-s-disease
#18
Andre F Batista, Leticia Forny-Germano, Julia R Clarke, Natalia M Lyra E Silva, Jordano Brito-Moreira, Susan E Boehnke, Andrew Winterborn, Brian C Coe, Ann Lablans, Juliana F Vital, Suelen A Marques, Ana Mb Martinez, Matthias Gralle, Christian Holscher, William L Klein, Jean-Christophe Houzel, Sergio T Ferreira, Douglas P Munoz, Fernanda G De Felice
Alzheimer's disease (AD) is a devastating neurological disorder that still lacks an effective treatment, and this has stimulated an intense pursuit of disease-modifying therapeutics. Given the increasingly recognized link between AD and defective brain insulin signaling, we investigated the actions of liraglutide, a glucagon-like peptide-1 (GLP-1) analog marketed for treatment of type 2 diabetes, in experimental models of AD. Insulin receptor pathology is an important feature of AD brains that impairs the neuroprotective actions of central insulin signaling...
May 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29421245/effect-of-glucagon-like-peptide-1-analogue-exendin-4-on-cognitive-functions-in-type-2-diabetes-mellitus-possible-modulation-of-brain-derived-neurotrophic-factor-and-brain-visfatin
#19
O M Abdelwahed, O M Tork, M M Gamal El Din, L Rashed, M Zickri
BACKGROUND: Brain derived neurotrophic factor (BDNF) is one of the most essential neurotrophic factors in the brain. BDNF is involved in learning, memory and locomotion suggesting it as a target in type 2 diabetes mellitus (T2DM) associated cognitive changes. Visfatin; an adipokine discovered to be expressed in the brain; was found to have multiple effects including its participation in keeping energy supply to the cell and is consequentially involved in cell survival. Its role in cognitive functions in T2DM was not studied before...
February 5, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29412810/glp-1-receptor-agonists-show-neuroprotective-effects-in-animal-models-of-diabetes
#20
Victor A Gault, Christian Hölscher
Enzyme-resistant receptor agonists of the incretin hormone glucagon-like peptide-1 (GLP-1) have shown positive therapeutic effects in people with type 2 diabetes mellitus (T2DM). T2DM has detrimental effects on brain function and impairment of cognition and memory formation has been described. One of the underlying mechanisms is most likely insulin de-sensitization in the brain, as insulin improves cognitive impairments and enhances learning. Treatment with GLP-1 receptor agonists improves memory formation and impairment of synaptic plasticity observed in animal models of diabetes-obesity...
February 2018: Peptides
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