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Agmatine ameliorates type 2 diabetes induced-Alzheimer's disease-like alterations in high-fat diet-fed mice via reactivation of blunted insulin signalling

Authors
 Somang Kang  ;  Chul-Hoon Kim  ;  Hosung Jung  ;  Eosu Kim  ;  Ho-Taek Song  ;  Jong Eun Lee 
Citation
 Neuropharmacology, Vol.113(Pt. A) : 467-479, 2017 
Journal Title
 Neuropharmacology 
ISSN
 0028-3908 
Issue Date
2017
MeSH
Agmatine/pharmacology ; Agmatine/therapeutic use* ; Alzheimer Disease/blood ; Alzheimer Disease/drug therapy* ; Alzheimer Disease/etiology ; Animals ; Blood Glucose/drug effects ; Blood Glucose/metabolism ; Brain/drug effects ; Brain/metabolism ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/drug therapy* ; Diabetes Mellitus, Type 2/etiology ; Diet, High-Fat/adverse effects* ; Insulin/metabolism* ; Insulin Resistance/physiology ; Male ; Maze Learning/physiology ; Mice ; Mice, Inbred ICR ; Random Allocation
Keywords
Agmatine ; Alzheimer's disease ; Brain insulin resistance ; High-fat diet
Abstract
The risk of Alzheimer's disease (AD) is higher in patients with type 2 diabetes mellitus (T2DM). Previous studies in high-fat diet-induced AD animal models have shown that brain insulin resistance in these animals leads to the accumulation of amyloid beta (Aβ) and the reduction in GSK-3β phosphorylation, which promotes tau phosphorylation to cause AD. No therapeutic treatments that target AD in T2DM patients have yet been discovered. Agmatine, a primary amine derived from l-arginine, has exhibited anti-diabetic effects in diabetic animals. The aim of this study was to investigate the ability of agmatine to treat AD induced by brain insulin resistance. ICR mice were fed a 60% high-fat diet for 12 weeks and received one injection of streptozotocin (100 mg/kg/ip) 4 weeks into the diet. After the 12-week diet, the mice were treated with agmatine (100 mg/kg/ip) for 2 weeks. Behaviour tests were conducted prior to sacrifice. Brain expression levels of the insulin signal molecules p-IRS-1, p-Akt, and p-GSK-3β and the accumulation of Aβ and p-tau were evaluated. Agmatine administration rescued the reduction in insulin signalling, which in turn reduced the accumulation of Aβ and p-tau in the brain. Furthermore, agmatine treatment also reduced cognitive decline. Agmatine attenuated the occurrence of AD in T2DM mice via the activation of the blunted insulin signal.
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DOI
10.1016/j.neuropharm.2016.10.029
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Psychiatry (정신과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
김어수(Kim, Eosu) ORCID logo https://orcid.org/0000-0001-9472-9465
김철훈(Kim, Chul Hoon) ORCID logo https://orcid.org/0000-0002-7360-429X
송호택(Song, Ho Taek) ORCID logo https://orcid.org/0000-0002-6655-2575
이종은(Lee, Jong Eun) ORCID logo https://orcid.org/0000-0001-6203-7413
정호성(Jung, Ho Sung) ORCID logo https://orcid.org/0000-0002-5059-8050
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/153419
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