PMID- 27810390
OWN - NLM
STAT- MEDLINE
DCOM- 20170711
LR  - 20180329
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 113
IP  - Pt A
DP  - 2017 Feb
TI  - Agmatine ameliorates type 2 diabetes induced-Alzheimer's disease-like alterations 
      in high-fat diet-fed mice via reactivation of blunted insulin signalling.
PG  - 467-479
LID - S0028-3908(16)30483-X [pii]
LID - 10.1016/j.neuropharm.2016.10.029 [doi]
AB  - 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 (Abeta) and the reduction in GSK-3beta 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-3beta and the accumulation 
      of Abeta and p-tau were evaluated. Agmatine administration rescued the reduction in 
      insulin signalling, which in turn reduced the accumulation of Abeta 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.
CI  - Copyright A(c) 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Kang, Somang
AU  - Kang S
AD  - Department of Anatomy, Yonsei University College of Medicine, Seoul, 120-752, 
      South Korea; BK21 Plus Project for Medical Sciences, and Brain Research 
      Institute, Yonsei University College of Medicine, Seoul, 120-752, South Korea.
FAU - Kim, Chul-Hoon
AU  - Kim CH
AD  - Department of Pharmacology, Yonsei University College of Medicine, Seoul, 
      120-752, South Korea.
FAU - Jung, Hosung
AU  - Jung H
AD  - Department of Anatomy, Yonsei University College of Medicine, Seoul, 120-752, 
      South Korea; BK21 Plus Project for Medical Sciences, and Brain Research 
      Institute, Yonsei University College of Medicine, Seoul, 120-752, South Korea.
FAU - Kim, Eosu
AU  - Kim E
AD  - Department of Psychiatry, Yonsei University College of Medicine, Seoul, 120-752, 
      South Korea.
FAU - Song, Ho-Taek
AU  - Song HT
AD  - Department of Diagnostic Radiology, Yonsei University College of Medicine, Seoul, 
      120-752, South Korea.
FAU - Lee, Jong Eun
AU  - Lee JE
AD  - Department of Anatomy, Yonsei University College of Medicine, Seoul, 120-752, 
      South Korea; BK21 Plus Project for Medical Sciences, and Brain Research 
      Institute, Yonsei University College of Medicine, Seoul, 120-752, South Korea. 
      Electronic address: jelee@yuhs.ac.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161031
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Blood Glucose)
RN  - 0 (Insulin)
RN  - 70J407ZL5Q (Agmatine)
SB  - IM
MH  - Agmatine/pharmacology/*therapeutic use
MH  - Alzheimer Disease/blood/*drug therapy/etiology
MH  - Animals
MH  - Blood Glucose/drug effects/metabolism
MH  - Brain/drug effects/metabolism
MH  - Diabetes Mellitus, Type 2/blood/*drug therapy/etiology
MH  - Diet, High-Fat/*adverse effects
MH  - Insulin/*metabolism
MH  - Insulin Resistance/physiology
MH  - Male
MH  - Maze Learning/physiology
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Random Allocation
OTO - NOTNLM
OT  - Agmatine
OT  - Alzheimer's disease
OT  - Brain insulin resistance
OT  - High-fat diet
EDAT- 2016/11/05 06:00
MHDA- 2017/07/14 06:00
CRDT- 2016/11/05 06:00
PHST- 2016/05/10 00:00 [received]
PHST- 2016/10/18 00:00 [revised]
PHST- 2016/10/28 00:00 [accepted]
PHST- 2016/11/05 06:00 [pubmed]
PHST- 2017/07/14 06:00 [medline]
PHST- 2016/11/05 06:00 [entrez]
AID - S0028-3908(16)30483-X [pii]
AID - 10.1016/j.neuropharm.2016.10.029 [doi]
PST - ppublish
SO  - Neuropharmacology. 2017 Feb;113(Pt A):467-479. doi: 
      10.1016/j.neuropharm.2016.10.029. Epub 2016 Oct 31.