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https://www.readbyqxmd.com/read/29032011/sitagliptin-enhances-the-neuroprotective-effect-of-pregabalin-against-pentylenetetrazole-induced-acute-epileptogenesis-in-mice-implication-of-oxidative-inflammatory-apoptotic-and-autophagy-pathways
#1
Manar A Nader, Hayam Ateyya, Mohamed El-Shafey, Nagla A El-Sherbeeny
The current investigation aimed at studying the anti-epileptogenic effect of sitagliptin. The possible effect of the drug in combination with pregabalin in pentylenetetrazole (PTZ)- induced seizures was studied. In addition, the postulated mechanisms that could mediate such effect were explored namely, suppression of oxidative stress and neuro-inflammatory markers, autophagy and apoptosis. Seven days prior to PTZ (60 mg/kg, sc) injection, mice were treated with sitagliptin (5, 15, and 60 mg/kg, twice daily, orally) or pregabalin (30 mg/kg, once daily, orally) or their combination...
October 11, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28991675/sodium-butyrate-exerts-protective-effect-against-parkinson-s-disease-in-mice-via-stimulation-of-glucagon-like-peptide-1
#2
Jiaming Liu, Fangyan Wang, Suzhi Liu, Jimei Du, Xuezhen Hu, Jiaojiao Xiong, Renchi Fang, Wenqian Chen, Jing Sun
Sodium butyrate (NaB) has exhibited protective activity in neurological disorders. Here, we investigated the neuroprotective effect and potential mechanisms of NaB in a mouse model of Parkinson's disease (PD). A mouse was intraperitoneally treated with MPTP (30mg/kg) for 7 consecutive days to induce PD model and NaB (200mg/kg) was intragastrically treated for 3weeks. The behavioral tests were then conducted. Dopaminergic degeneration was evaluated by western blot and immunohistochemistry of tyrosine hydroxylase (TH) in the SN...
October 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28986282/exendin-4-attenuates-neuronal-death-via-glp-1r-pi3k-akt-pathway-in-early-brain-injury-after-subarachnoid-hemorrhage-in-rats
#3
Zhiyi Xie, Budbazar Enkhjargal, Lingyun Wu, Keren Zhou, Chengmei Sun, Xin Hu, Vadim Gospodarev, Jiping Tang, Chao You, John H Zhang
Neuronal apoptosis is considered to be a crucial therapeutic target against early brain injury (EBI) after subarachnoid hemorrhage (SAH). Emerging evidence indicates that Exendin-4 (Ex-4), a glucagon-like peptide 1 receptor (GLP-1R) agonist, plays a neuroprotective role in cerebrovascular disease. This study was conducted in order to verify the neuroprotective role of EX-4 in EBI after SAH in rats. The endovascular perforation model of SAH was performed in Sprague-Dawley rats (n = 153). Ex-4 was intraperitoneally injected 1 h after SAH induction in the rats (SAH + Ex-4)...
October 4, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28912645/anti-inflammatory-effect-of-glucagon-like-peptide-1-receptor-agonist-exendin-4-through-modulation-of-ib1-jip1-expression-and-jnk-signaling-in-stroke
#4
Soojin Kim, Jaewon Jeong, Hye-Seon Jung, Bokyung Kim, Ye-Eun Kim, Da-Sol Lim, So-Dam Kim, Yun Seon Song
Glucagon like peptide-1 (GLP-1) stimulates glucose-dependent insulin secretion. Dipeptidyl peptidase-4 (DPP-4) inhibitors, which block inactivation of GLP-1, are currently in clinical use for type 2 diabetes mellitus. Recently, GLP-1 has also been reported to have neuroprotective effects in cases of cerebral ischemia. We therefore investigated the neuroprotective effects of GLP-1 receptor (GLP-1R) agonist, exendin-4 (ex-4), after cerebral ischemia-reperfusion injury. Transient middle cerebral artery occlusion (tMCAO) was induced in rats by intracerebroventricular (i...
August 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28894301/lateral-hypothalamic-glp-1-receptors-are-critical-for-the-control-of-food-reinforcement-ingestive-behavior-and-body-weight
#5
L López-Ferreras, J E Richard, E E Noble, K Eerola, R H Anderberg, K Olandersson, L Taing, S E Kanoski, M R Hayes, K P Skibicka
Increased motivation for highly rewarding food is a major contributing factor to obesity. Most of the literature focuses on the mesolimbic nuclei as the core of reward behavior regulation. However, the lateral hypothalamus (LH) is also a key reward-control locus in the brain. Here we hypothesize that manipulating glucagon-like peptide-1 receptor (GLP-1R) activity selectively in the LH can profoundly affect food reward behavior, ultimately leading to obesity. Progressive ratio operant responding for sucrose was examined in male and female rats, following GLP-1R activation and pharmacological or genetic GLP-1R blockade in the LH...
September 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28881865/insulinotropic-actions-of-glp-1-how-much-in-the-brain-and-how-much-in-the-periphery
#6
Eva Tudurí, Ruben Nogueiras
No abstract text is available yet for this article.
July 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28867303/treatment-with-a-glp-1r-agonist-over-four-weeks-promotes-weight-loss-moderated-changes-in-frontal-striatal-brain-structures-in-individuals-with-mood-disorders
#7
Rodrigo B Mansur, Andre Zugman, Juhie Ahmed, Danielle S Cha, Mehala Subramaniapillai, Yena Lee, Julie Lovshin, Jung G Lee, Jae-Hon Lee, Vladislav Drobinin, Jason Newport, Elisa Brietzke, Eva Z Reininghaus, Kang Sim, Maj Vinberg, Natalie Rasgon, Tomas Hajek, Roger S McIntyre
Cognitive deficits are a core feature across psychiatric disorders. Emerging evidence indicates that metabolic pathways are highly relevant for the substrates and phenomenology of the cognitive domain. Herein, we aimed to determine the effects of liraglutide, a GLP-1R agonist, on brain structural/volumetric parameters in adults with a mood disorder. This is the secondary analysis of a 4-week, pilot, proof-of-concept, open-label study. Participants (N=19) exhibiting impairments in executive function with either major depressive disorder (MDD) or bipolar disorder (BD) were recruited...
August 31, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28833775/glucagon-like-peptide-1-cleavage-product-glp-1-9-36-amide-enhances-hippocampal-long-term-synaptic-plasticity-in-correlation-with-suppression-of-kv4-2-expression-and-eef2-phosphorylation
#8
Stephen M Day, Wenzhong Yang, Sarah Ewin, Xueyan Zhou, Tao Ma
Glucagon-like peptide-1 (GLP-1) is an endogenous gut hormone and a key regulator in maintaining glucose homeostasis by stimulating insulin secretion. Its natural cleavage product GLP-1 (9-36), used to be considered a "bio-inactive" metabolite mainly due to its lack of insulinotropic effects and low affinity for GLP-1 receptors, possesses unique properties such as anti-oxidant and cardiovascular protection. Little is known about the role of GLP-1 (9-36) in central nervous system. Here we report that chronic, systemic application of GLP-1 (9-36) in adult mice facilitated both the induction and maintenance phases of hippocampal Long-term potentiation (LTP), a major form of synaptic plasticity...
August 18, 2017: Hippocampus
https://www.readbyqxmd.com/read/28827991/anticonvulsant-effect-of-liraglutide-glp-1-agonist-by-averting-a-change-in-gaba-and-brain-glutathione-level-on-picrotoxin-induced-seizures
#9
Gaurav Gupta, Rajiv Dahiya, Kamal Dua, Dinesh Kumar Chellappan, Juhi Tiwari, Ganesh Narayan Sharma, Santosh Kumar Singh, Anurag Mishra, Rakesh Kumar Sharma, Mohit Agrawal
No abstract text is available yet for this article.
2017: EXCLI journal
https://www.readbyqxmd.com/read/28781108/exenatide-once-weekly-versus-placebo-in-parkinson-s-disease-a-randomised-double-blind-placebo-controlled-trial
#10
Dilan Athauda, Kate Maclagan, Simon S Skene, Martha Bajwa-Joseph, Dawn Letchford, Kashfia Chowdhury, Steve Hibbert, Natalia Budnik, Luca Zampedri, John Dickson, Yazhou Li, Iciar Aviles-Olmos, Thomas T Warner, Patricia Limousin, Andrew J Lees, Nigel H Greig, Susan Tebbs, Thomas Foltynie
BACKGROUND: Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has neuroprotective effects in preclinical models of Parkinson's disease. We investigated whether these effects would be apparent in a clinical trial. METHODS: In this single-centre, randomised, double-blind, placebo-controlled trial, patients with moderate Parkinson's disease were randomly assigned (1:1) to receive subcutaneous injections of exenatide 2 mg or placebo once weekly for 48 weeks in addition to their regular medication, followed by a 12-week washout period...
August 3, 2017: Lancet
https://www.readbyqxmd.com/read/28761132/exendin-4-reduces-food-intake-via-the-pi3k-akt-signaling-pathway-in-the-hypothalamus
#11
Yan Yang, Pique P Choi, Wanli W Smith, Weijie Xu, Delin Ma, Zachary A Cordner, Nu-Chu Liang, Timothy H Moran
Exendin-4 (EX-4), a glucagon-like peptide-1 (GLP-1) receptor agonist, has been shown to reduce food intake and to increase proopiomelanocortin (POMC) gene expression in the hypothalamus. In this study, we examined the potential neural mechanisms by which these effects occur. Male Sprague Dawley rats were implanted with a cannula in the third ventricle of the brain through which an inhibitor of phosphatidylinositol-3 kinase (PI3K) (wortmannin) was administered, and EX-4 or vehicle was administered via intraperitoneal (IP) injection...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28757640/effects-of-peripheral-administration-of-a-neuromedin-u-receptor-2-selective-agonist-on-food-intake-and-body-weight-in-obese-mice
#12
T Kaisho, H Nagai, T Asakawa, N Suzuki, H Fujita, K Matsumiya, N Nishizawa, Y Kanematsu-Yamaki, K Dote, J-I Sakamoto, T Asami, S Takekawa
BACKGROUND: Neuromedin U (NMU) is a neuropeptide with various physiological functions including regulation of smooth-muscle contraction, blood pressure, stress responses, and feeding behaviors. NMU activates two distinct receptors, NMUR1 and NMUR2, which are predominantly expressed in peripheral tissues and the central nervous system, respectively. It is reported that the NMU signaling system regulates food intake and body weight via NMUR2, suggesting that an NMUR2 agonist exhibiting anorectic effects would be a potential therapy for obesity...
July 31, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28752054/serotonergic-modulation-of-the-activity-of-glp-1-producing-neurons-in-the-nucleus-of-the-solitary-tract-in-mouse
#13
Marie K Holt, Ida J Llewellyn-Smith, Frank Reimann, Fiona M Gribble, Stefan Trapp
OBJECTIVE: Glucagon-like peptide-1 (GLP-1) and 5-HT are potent regulators of food intake within the brain. GLP-1 is expressed by preproglucagon (PPG) neurons in the nucleus tractus solitarius (NTS). We have previously shown that PPG neurons innervate 5-HT neurons in the ventral brainstem. Here, we investigate whether PPG neurons receive serotonergic input and respond to 5-HT. METHODS: We employed immunohistochemistry to reveal serotonergic innervation of PPG neurons...
August 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28747063/dpp4-inhibitors-can-be-a-drug-of-choice-for-type-3-diabetes-a-mini-review
#14
Nehru Sai Suresh Chalichem, Chaitanya Gonugunta, Praveen Thaggikuppe Krishnamurthy, Basavan Duraiswamy
As well known to the scientific community, Alzheimer's disease (AD) is an irreversible neurodegenerative disease that ends up with impairment of memory and cognition due to neuronal and synapse loss. Patient's quality of life can be enhanced by targeting neurogenesis as a therapeutic paradigm. Moreover, several research evidences support the concept that AD is a type of metabolic disorder mediated by impairment in brain insulin responsiveness and energy metabolism. Growing evidence suggests that endogenous peptides such as glucagon-like peptide-1 (GLP-1) and stromal-derived factor-1α (SDF-1α) provide neuroprotection across a range of experimental models of AD...
January 1, 2017: American Journal of Alzheimer's Disease and Other Dementias
https://www.readbyqxmd.com/read/28724607/renal-hemodynamic-effects-of-glucagon-like-peptide-1-agonist-are-mediated-by-nitric-oxide-but-not-prostaglandin
#15
Scott Culver Thomson, Ali Kashkouli, Zhi Zhao Liu, Prabhleen Singh
The incretin hormone, glucagon like peptide-1 (GLP-1), is known for responding to dietary fat and carbohydrate. It elicits effects on pancreas, gut, and brain to stabilize blood glucose levels. We have previously reported that the GLP-1 agonist, exenatide, vasodilates the kidney and suppresses proximal reabsorption. The present study was undertaken to determine whether the renal effects of exenatide are mediated by nitric oxide (NO) and/or prostaglandins. Inulin clearance (GFR) and urine flow rate (UV) were measured in anesthetized rats before and during exenatide infusion (1 nmol/h iv)...
July 19, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28717164/glucagon-like-peptide-1-reduces-pancreatic-%C3%AE-cell-mass-through-hypothalamic-neural-pathways-in-high-fat-diet-induced-obese-rats
#16
Hisae Ando, Koro Gotoh, Kansuke Fujiwara, Manabu Anai, Seiichi Chiba, Takayuki Masaki, Tetsuya Kakuma, Hirotaka Shibata
We examined whether glucagon-like peptide-1 (GLP-1) affects β-cell mass and proliferation through neural pathways, from hepatic afferent nerves to pancreatic efferent nerves via the central nervous system, in high-fat diet (HFD)-induced obese rats. The effects of chronic administration of GLP-1 (7-36) and liraglutide, a GLP-1 receptor agonist, on pancreatic morphological alterations, c-fos expression and brain-derived neurotrophic factor (BDNF) content in the hypothalamus, and glucose metabolism were investigated in HFD-induced obese rats that underwent hepatic afferent vagotomy (VgX) and/or pancreatic efferent sympathectomy (SpX)...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28710180/dipeptidyl-peptidase-4-regulates-hematopoietic-stem-cell-activation-in-response-to-chronic-stress
#17
Enbo Zhu, Lina Hu, Hongxian Wu, Limei Piao, Guangxian Zhao, Aiko Inoue, Weon Kim, Chenglin Yu, Wenhu Xu, Yasuko K Bando, Xiang Li, Yanna Lei, Chang-Ning Hao, Kyosuke Takeshita, Woo-Shik Kim, Kenji Okumura, Toyoaki Murohara, Masafumi Kuzuya, Xian Wu Cheng
BACKGROUND: DPP4 (Dipeptidyl peptidase-4)-GLP-1 (glucagon-like peptide-1) and its receptor (GLP-1R) axis has been involved in several intracellular signaling pathways. The Adrβ3 (β3-adrenergic receptor)/CXCL12 (C-X-C motif chemokine 12) signal was required for the hematopoiesis. We investigated the novel molecular requirements between DPP4-GLP-1/GLP-1 and Adrβ3/CXCL12 signals in bone marrow (BM) hematopoietic stem cell (HSC) activation in response to chronic stress. METHODS AND RESULTS: Male 8-week-old mice were subjected to 4-week intermittent restrain stress and orally treated with vehicle or the DPP4 inhibitor anagliptin (30 mg/kg per day)...
July 14, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28702330/neonatal-glp1r-activation-limits-adult-adiposity-by-durably-altering-hypothalamic-architecture
#18
Andrea V Rozo, Daniella A Babu, PoMan A Suen, David N Groff, Randy J Seeley, Rebecca A Simmons, Patrick Seale, Rexford S Ahima, Doris A Stoffers
OBJECTIVE: Adult obesity risk is influenced by alterations to fetal and neonatal environments. Modifying neonatal gut or neurohormone signaling pathways can have negative metabolic consequences in adulthood. Here we characterize the effect of neonatal activation of glucagon like peptide-1 (GLP-1) receptor (GLP1R) signaling on adult adiposity and metabolism. METHODS: Wild type C57BL/6 mice were injected with 1 nmol/kg Exendin-4 (Ex-4), a GLP1R agonist, for 6 consecutive days after birth...
July 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28698254/mechanism-based-pharmacokinetic-pharmacodynamic-modeling-of-the-glucagon-like-peptide-1-receptor-agonist-exenatide-to-characterize-its-antiobesity-effects-in-diet-induced-obese-mice
#19
Shinji Iwasaki, Teruki Hamada, Ikumi Chisaki, Tomohiro Andou, Noriyasu Sano, Atsutoshi Furuta, Nobuyuki Amano
In addition to their potent antidiabetic effects, glucagon-like peptide-1 (GLP-1) analogs lower body weight in humans. Hence, agonistic targeting of the GLP-1 receptor could be a valid approach to target obesity. However, quantitative analyses of the pharmacokinetic/pharmacodynamic (PK/PD) relationship between GLP-1 analogs and their antiobesity effect have not been reported in either animals or humans. Therefore, the present study was performed to establish a mechanism-based PK/PD model of GLP-1 receptor agonists using the GLP-1 analog exenatide for the development of promising new antiobesity drugs...
September 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28685025/gut-hormones-such-as-amylin-and-glp-1-in-the-control-of-eating-and-energy-expenditure
#20
REVIEW
T A Lutz
The control of meal size is the best studied aspect of the control of energy balance, and manipulation of this system constitutes a promising target to treat obesity. A major part of this control system is based on gastrointestinal hormones such as glucagon-like peptide-1 (GLP-1) or amylin, which are released in response to a meal and which limit the size of an ongoing meal. Both amylin and GLP-1 have also been shown to increase energy expenditure in experimental rodents, but mechanistically we know much less how this effect may be mediated, which brain sites may be involved, and what the physiological relevance of these findings may be...
December 2016: International Journal of Obesity Supplements
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