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GLP-1 Neuroprotection

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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
#1
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/29765322/therapeutic-potential-of-ginsenosides-as-an-adjuvant-treatment-for-diabetes
#2
REVIEW
Litao Bai, Jialiang Gao, Fan Wei, Jing Zhao, Danwei Wang, Junping Wei
Ginseng, one of the oldest traditional Chinese medicinal herbs, has been used widely in China and Asia for thousands of years. Ginsenosides extracted from ginseng, which is derived from the roots and rhizomes of Panax ginseng C. A. Meyer, have been used in China as an adjuvant in the treatment of diabetes mellitus. Owing to the technical complexity of ginsenoside production, the total ginsenosides are generally extracted. Accumulating evidence has shown that ginsenosides exert antidiabetic effects. In vivo and in vitro tests revealed the potential of ginsenoside Rg1, Rg3, Rg5, Rb1, Rb2, Rb3, compound K, Rk1, Re, ginseng total saponins, malonyl ginsenosides, Rd, Rh2, F2, protopanaxadiol (PPD) and protopanaxatriol (PPT)-type saponins to treat diabetes and its complications, including type 1 diabetes mellitus, type 2 diabetes mellitus, diabetic nephropathy, diabetic cognitive dysfunction, type 2 diabetes mellitus with fatty liver disease, diabetic cerebral infarction, diabetic cardiomyopathy, and diabetic erectile dysfunction...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29705602/liraglutide-attenuates-the-depressive-and-anxiety-like-behaviour-in-the-corticosterone-induced-depression-model-via-improving-hippocampal-neural-plasticity
#3
Han Weina, Niu Yuhu, Holscher Christian, Li Birong, Shen Feiyu, Wang Le
Recent studies indicate that metabolic disorders such as diabetes and obesity are a major risk factor of psychiatric diseases. This relationship opens the opportunity to develop new antidepressant drugs by repurposing antidiabetic drugs. Previous research has demonstrated that GLP-1 analogs are neuroprotective in several neurological disease models including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. In addition, the GLP-1 analog liraglutide has been shown to promote neurogenesis, which is seen to play important roles in memory formation and cognitive and emotional processing...
April 26, 2018: Brain Research
https://www.readbyqxmd.com/read/29671019/lixisenatide-a-novel-glp-1-analog-protects-against-cerebral-ischemia-reperfusion-injury-in-diabetic-rats
#4
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/29626654/geniposide-improves-repeated-restraint-stress-induced-depression-like-behavior-in-mice-by-ameliorating-neuronal-apoptosis-via-regulating-glp-1r-akt-signaling-pathway
#5
Yinghua Zhao, Hongyan Li, Fang Fang, Tingting Qin, Wei Xiao, Zhenzhong Wang, Shiping Ma
Geniposide (GP), a bioactive iridoid glycoside isolated from Gardenia jasminoides Ellis, as well as an agonist of Glucagon-like peptide-1 receptor (GLP-1R), has been reported to exhibit antidepressant-like effects in several rodent models. However, the underlying mechanisms remain obscure. In this study, we mainly investigated the antidepressant-like effects of GP and explored the possible mechanisms associated with GLP-1R signaling by using the repeated restraint stress (RRS)-induced depression model of mice...
April 4, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29551659/da5-ch-a-novel-glp-1-gip-dual-agonist-effectively-ameliorates-the-cognitive-impairments-and-pathology-in-the-app-ps1-mouse-model-of-alzheimer-s-disease
#6
Yue Cao, Christian Hölscher, Meng-Ming Hu, Ting Wang, Fang Zhao, Yu Bai, Jun Zhang, Mei-Na Wu, Jin-Shun Qi
Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which there is no cure. The early primary symptom of AD is the decline of memory ability, which gradually develops into complete dementia. Type 2 diabetes mellitus (T2DM) is an important risk factor of AD; and mimetics of the incretin hormone GLP-1 developed to treat diabetes are being tested as a novel therapeutic strategy for AD. In the present study, we reported for the first time the neuroprotective effects of a novel GLP-1/GIP dual agonist DA5-CH that activates the incretin hormone GLP-1 and GIP receptors in the APP/PS1 transgenic AD mouse model...
March 15, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29549796/post-treatment-with-the-glp-1-analogue-liraglutide-alleviate-chronic-inflammation-and-mitochondrial-stress-induced-by-status-epilepticus
#7
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/29501615/glucagon-like-peptide-1-mediates-effects-of-oral-galactose-in-streptozotocin-induced-rat-model-of-sporadic-alzheimer-s-disease
#8
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/29493378/liraglutide-prevents-metabolic-side-effects-and-improves-recognition-and-working-memory-during-antipsychotic-treatment-in-rats
#9
Ilijana Babic, Ashleigh Gorak, Martin Engel, Dominic Sellers, Paul Else, Ashleigh L Osborne, Nagesh Pai, Xu-Feng Huang, Jessica Nealon, Katrina Weston-Green
BACKGROUND: Antipsychotic drugs (APDs), olanzapine and clozapine, do not effectively address the cognitive symptoms of schizophrenia and can cause serious metabolic side-effects. Liraglutide is a synthetic glucagon-like peptide-1 (GLP-1) receptor agonist with anti-obesity and neuroprotective properties. The aim of this study was to examine whether liraglutide prevents weight gain/hyperglycaemia side-effects and cognitive deficits when co-administered from the commencement of olanzapine and clozapine treatment...
May 2018: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/29481915/cognitive-dysfunction-and-metabolic-comorbidities-in-mood-disorders-a-repurposing-opportunity-for-glucagon-like-peptide-1-receptor-agonists
#10
REVIEW
Rodrigo B Mansur, Yena Lee, Mehala Subramaniapillai, Elisa Brietzke, Roger S McIntyre
Major depressive disorder and bipolar disorder are highly prevalent and disabling conditions. Cognition is considered a core domain of their psychopathology and a principle mediator of psychosocial impairment, disproportionately accounting for overall illness-associated costs. There are few interventions with replicated evidence of efficacy in treating cognitive deficits in mood disorders. Evidence also indicates that cognitive deficits are associated with obesity and involve significant impairment across multiple domains...
February 23, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29473979/a-novel-glp-1-gip-gcg-triagonist-reduces-cognitive-deficits-and-pathology-in-the-3xtg-mouse-model-of-alzheimer-s-disease
#11
Tian Li, Juan-Juan Jiao, Christian Hölscher, Mei-Na Wu, Jun Zhang, Jia-Qing Tong, Xue-Fan Dong, Xue-Song Qu, Yue Cao, Hong-Yan Cai, Qiang Su, Jin-Shun Qi
Type 2 diabetes mellitus (T2DM) is an important risk factor for Alzheimer's disease (AD). Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have been identified to be effective in T2DM treatment and neuroprotection. In this study, we further explored the effects of a novel unimolecular GLP-1/GIP/Gcg triagonist on the cognitive behavior and cerebral pathology in the 7-month-old triple transgenic mouse model of AD (3xTg-AD), and investigated its possible electrophysiological and molecular mechanisms...
May 2018: Hippocampus
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
#12
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
#13
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/29412810/glp-1-receptor-agonists-show-neuroprotective-effects-in-animal-models-of-diabetes
#14
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
https://www.readbyqxmd.com/read/29411931/neuroprotective-mechanisms-of-glucagon-like-peptide-1-based-therapies-in-ischaemic-stroke-a-systematic-review-based-on-pre-clinical-studies
#15
REVIEW
Ida R Marlet, Joakim N E Ölmestig, Tina Vilsbøll, Jørgen Rungby, Christina Kruuse
Glucagon-like peptide-1 (GLP-1)-based therapies, GLP-1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase-4 inhibitors (DPP-4Is) are widely used for the treatment of type 2 diabetes. Increasing evidence suggests that they may provide neuroprotection. The aim of this MiniReview was to systematically evaluate the proposed mechanism of action for GLP-1-based therapies in ischaemic brain damage in animals. We performed a literature search using MEDLINE, EMBASE and The Cochrane Library. GLP-1-based therapies administered before, during or after experimental stroke in diabetic and non-diabetic animals were evaluated...
February 7, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29402504/novel-dual-glp-1-gip-receptor-agonists-show-neuroprotective-effects-in-alzheimer-s-and-parkinson-s-disease-models
#16
REVIEW
Christian Hölscher
Type 2 diabetes is a risk factor for several chronic neurodegenerative disorders such as Alzheimer's or Parkinson's disease. The link appears to be insulin de-sensitisation in the brain. Insulin is an important neuroprotective growth factor. GLP-1 and GIP are growth factors that re-sensitise insulin and GLP-1 mimetics are used in the clinic to treat diabetes. GLP-1 and GIP mimetics initially designed to treat diabetes show good protective effects in animal models of Alzheimer's and Parkinson's disease. Based on these results, several clinical trials have shown first encouraging effects in patients with Alzheimer's or Parkinson' disease...
January 31, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29395648/delayed-administration-of-the-glucagon-like-peptide-1-analog-liraglutide-promoting-angiogenesis-after-focal-cerebral-ischemia-in-mice
#17
Yanxia Chen, Xiangjian Zhang, Junna He, Yanzhao Xie, Yang Yang
BACKGROUND: Glucagon-like peptide 1 (GLP-1) analogs administered before or after cerebral ischemia have been shown to provide neuroprotection. Here, we explored whether delayed administration of a GLP-1 analog, liraglutide, could improve long-term functional recovery and promote angiogenesis after stroke. MATERIALS AND METHODS: In the present study, mice were established as a focal cerebral cortical ischemia model and were intraperitoneally administered liraglutide or normal saline (NS) daily for 14 consecutive days, starting 1 day after cerebral ischemia...
May 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/29329976/therapeutic-potential-of-spinal-glp-1-receptor-signaling
#18
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...
March 2018: Peptides
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
#19
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...
March 15, 2018: 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
#20
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
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