Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jun 25, 2015; 6(6): 807-827
Published online Jun 25, 2015. doi: 10.4239/wjd.v6.i6.807
Gut-brain connection: The neuroprotective effects of the anti-diabetic drug liraglutide
Emanuel Monteiro Candeias, Inês Carolina Sebastião, Susana Maria Cardoso, Sónia Catarina Correia, Cristina Isabel Carvalho, Ana Isabel Plácido, Maria Sancha Santos, Catarina Resende Oliveira, Paula Isabel Moreira, Ana Isabel Duarte
Emanuel Monteiro Candeias, Inês Carolina Sebastião, Susana Maria Cardoso, Cristina Isabel Carvalho, Ana Isabel Plácido, Maria Sancha Santos, Catarina Resende Oliveira, Paula Isabel Moreira, Ana Isabel Duarte, Sónia Correia Correia, CNC - Center for Neuroscience and Cell Biology, Rua Larga, Faculty of Medicine (1st Floor), University of Coimbra, 3004-517 Coimbra, Portugal
Emanuel Monteiro Candeias, Inês Carolina Sebastião, Susana Maria Cardoso, Sónia Catarina Correia, Cristina Isabel Carvalho, Ana Isabel Duarte, Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Casa Costa Alemão - Pólo II, Rua D Francisco de Lemos, 3030-789 Coimbra, Portugal
Ana Isabel Plácido, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal
Maria Sancha Santos, Life Sciences Department, University of Coimbra, Largo Marquês de Pombal, 3004-517 Coimbra, Portugal
Catarina Resende Oliveira, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal
Paula Isabel Moreira, Institute of Physiology, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal
Author contributions: Candeias EM and Sebastião IC performed the literature search, wrote the text and draw Table 1; Cardoso SM, Correia SC, Carvalho CI, Plácido AI and Santos MS draw the figures; Oliveira CR, Moreira PI and Duarte AI suggested the theme to be reviewed, designed the text structure and made the several critical corrections and revisions until the submitted version was achieved.
Supported by FEDER (Programa Operacional Factores de Competitividade - COMPETE) and Portuguese funds via Portuguese Science Foundation (FCT) (Projects: PTDC/SAU-NMC/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 DoIT, “DIAMARKER PROJECT”, n.º 13853, SFRH/BD/73388/2010, SFRH/BPD/84473/2012).
Conflict-of-interest: The above-mentioned authors of this manuscript hereby declare that they do not have any conflict-of-interest (including but not limited to commercial, personal, political, intellectual, or religious interests) related to the work submitted herein.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Ana Isabel Duarte, CNC - Center for Neuroscience and Cell Biology, Rua Larga, Faculty of Medicine (1st Floor), University of Coimbra, Largo Marquês de Pombal, 3004-517 Coimbra, Portugal. anaimduarte@gmail.com
Telephone: +351-239-820190 Fax: +351-239-822776
Received: November 17, 2014
Peer-review started: November 17, 2014
First decision: December 12, 2014
Revised: May 4, 2015
Accepted: May 16, 2015
Article in press: May 18, 2015
Published online: June 25, 2015
Core Tip

Core tip: Glucagon-like peptide-1 (GLP-1) physiological responses are dependent on a gut-brain axis and receptor (GLP-1R) activation. GLP-1Rs are widely expressed throughout the body, including several brain areas. GLP-1 may readily diffuse across the blood-brain-barrier, activating neuroprotective pathways. Given the native GLP-1 short half-life, liraglutide has been developed with a highly increased half-life, allowing its use to treat type 2 diabetes (T2D). Given T2D patients increased risk for obesity and dementia [e.g., Alzheimer disease (AD)], and evidence from preclinical studies, whereby liraglutide showed impressive neuroprotective effects, clinical studies are underway to test the role of liraglutide on weigh control and AD.