Document Detail


Four weeks administration of Liraglutide improves memory and learning as well as glycaemic control in mice with high fat dietary-induced obesity and insulin resistance.
MedLine Citation:
PMID:  20920042     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIM: Liraglutide is a long-acting glucagon-like peptide-1 (GLP-1) mimetic which is a treatment option for type 2 diabetes. GLP-1 peptides, including Liraglutide, cross the blood-brain barrier and may additionally act to improve brain function. The present study tested the hypothesis that, in addition to its antihyperglycaemic actions, peripheral administration of Liraglutide exerts positive actions on cognitive function in mice with high fat dietary-induced obesity and insulin resistance.
METHODS: Young Swiss TO mice maintained on high fat diet for 20 weeks received twice-daily injections of Liraglutide (200 µg/kg bw; sc) or saline vehicle over 28 days. An additional group of mice on standard diet received twice-daily saline injections. Energy intake, bodyweight, non-fasting plasma glucose and insulin concentrations were monitored at regular intervals. Glucose tolerance, open field assessment, object recognition testing and electrophysiological long-term potentiation (LTP) were performed at termination of the study.
RESULTS: Liraglutide treatment resulted in significant time-dependent reduction in bodyweight and energy intake, whilst improving non-fasting glucose and normalizing glucose tolerance. Although Liraglutide did not alter general behaviour, treated mice exhibited marked increase in recognition index (RI) during object recognition testing, indicative of enhanced learning and memory ability. Furthermore, Liraglutide rescued the deleterious effects of high fat diet on hippocampal LTP of neurotransmission following both chronic and direct intracerebroventricular (icv) administration.
CONCLUSION: Liraglutide administered peripherally not only improves metabolic parameters but exerts additional beneficial effects on cognitive function and hippocampal synaptic plasticity. Whether therapy with GLP-1 mimetics has similar effects in humans with type 2 diabetes needs to be established.
Authors:
D W Porter; B D Kerr; P R Flatt; C Holscher; V A Gault
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Diabetes, obesity & metabolism     Volume:  12     ISSN:  1463-1326     ISO Abbreviation:  Diabetes Obes Metab     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-05     Completed Date:  2011-06-02     Revised Date:  2013-05-13    
Medline Journal Info:
Nlm Unique ID:  100883645     Medline TA:  Diabetes Obes Metab     Country:  England    
Other Details:
Languages:  eng     Pagination:  891-9     Citation Subset:  IM    
Copyright Information:
© 2010 Blackwell Publishing Ltd.
Affiliation:
The SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Glucose / drug effects*
Cognition / drug effects*,  physiology
Diabetes Mellitus, Type 2
Glucagon-Like Peptide 1 / administration & dosage,  analogs & derivatives*
Hypoglycemic Agents / administration & dosage*
Insulin Resistance / physiology
Male
Memory / drug effects*,  physiology
Mice
Obesity / drug therapy*
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Hypoglycemic Agents; 839I73S42A/liraglutide; 89750-14-1/Glucagon-Like Peptide 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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