Gut-brain connection: The neuroprotective effects of the anti-diabetic drug liraglutide

查看全文 作　　者：Emanuel Monteiro [1,2]Candeias;Inês Carolina Sebasti[1,2]o;Susana Maria [1,2]Cardoso;Sónia Catarina [1,2]Correia;Cristina Isabel [1,2]Carvalho;Ana Isabel [1,3]Plácido;Maria Sancha [1,4]Santos;Catarina Resende [1,5]Oliveira;Paula Isabel [1,6]Moreira;Ana Isabel [1,2]Duarte

机构地区：[1]CNC-Center for Neuroscience and Cell Biology, Rua Larga, Faculty of Medicine (1st Floor), University of Coimbra;[2]Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Casa Costa Alem?o-Pólo II, Rua D Francisco de Lemos, 3030-789 Coimbra, Portugal;[3]Faculty of Medicine, University of Coimbra;[4]Life Sciences Department, University of Coimbra, Largo Marquês de Pombal, 3004-517 Coimbra, Portugal;[5]Institute of Biochemistry, Faculty of Medicine, University of Coimbra;[6]Institute of Physiology, Faculty of Medicine, University of Coimbra

出　　处：《World Journal of Diabetes》索引2015年第6卷第6期,共21页

基　　金：Supported by FEDER(Programa Operacional Factores de Competitividade-COMPETE);Portuguese funds via Portuguese Science Foundation(FCT)(Projects:PTDC/SAUNMC/110990/2009,PTDC/SAU-TOX/117481/2010 and Pest/SAU/LA0001/2011;fellowships:SFRH/BD/90036/2012,PTDC/SAU-TOX/117481/2010,SFRH/BPD/95770/2013,SFRH/BPD/84163/2012,QREN Do IT,'DIAMARKER PROJECT',n.o 13853,SFRH/BD/73388/2010,SFRH/BPD/84473/2012) 摘　　要：Long-acting glucagon-like peptide-1(GLP-1) analogues marketed for type 2 diabetes(T2D) treatment have been showing positive and protective effects in several different tissues, including pancreas, heart or even brain. This gut secreted hormone plays a potent insulinotropic activity and an important role in maintaining glucose homeostasis. Furthermore, growing evidences suggest the occurrence of several commonalities between T2 D and neurodegenerative diseases, insulin resistance being pointed as a main cause for cognitive decline and increased risk to develop dementia. In this regard, it has also been suggested that stimulation of brain insulin signaling may have a protective role against cognitive deficits. As GLP-1 receptors(GLP-1R) are expressed throughout the central nervous system and GLP-1 may cross the blood-brain-barrier, an emerging hypothesis suggests that they may be promising therapeutic targets against brain dysfunctional insulin signaling-related pathologies. Importantly, GLP-1 actions depend not only on the direct effect mediated by its receptor activation, but also on the gut-brain axis involving an exchange of signals between both tissues via the vagal nerve, thereby regulating numerous physiological functions(e.g., energy homeostasis, glucose-dependent insulin secretion, as well as appetite and weight control). Amongst the incretin/GLP-1 mimetics class of anti-T2 D drugs with an increasingly described neuroprotective potential, the already marketed liraglutide emerged as a GLP-1R agonist highly resistant to dipeptidyl peptidase-4 degradation(thereby having an increased half-life) and whose systemic GLP-1R activity is comparable to that of native GLP-1. Importantly, several preclinical studies showed anti-apoptotic, anti-inflammatory, anti-oxidant and neuroprotective effects of liraglutide against T2 D, stroke and Alzheimer disease(AD), whereas several clinical trials, demonstrated some surprising benefits of liraglutide on weight loss, microglia inhibition, behavior and cognition, and in AD biomarkers. Herein, we discuss the GLP-1 action through the gut-brain axis, the hormone's regulation of some autonomic functions and liraglutide's neuroprotective potential. 关键词：Type 2 diabetes Glucagon-like peptide-1 GUT Brain Insulin LIRAGLUTIDE ALZHEIMER disease NEUROPROTECTION

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Gut-brain connection: The neuroprotective effects of the anti-diabetic drug liraglutide

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