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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.
Files in This Item:
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DOI
10.1016/j.neuropharm.2016.10.029
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Psychiatry (정신과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Eosu(김어수) ORCID logo https://orcid.org/0000-0001-9472-9465
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Song, Ho Taek(송호택) ORCID logo https://orcid.org/0000-0002-6655-2575
Lee, Jong Eun(이종은) ORCID logo https://orcid.org/0000-0001-6203-7413
Jung, Ho Sung(정호성) ORCID logo https://orcid.org/0000-0002-5059-8050
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/153419
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