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

Neuropharmacology
Somang KangJong Eun Lee

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 r...Continue Reading

References

Jun 24, 1982·Nature·R G MorrisJ O'Keefe
May 30, 2001·Molecular and Cellular Endocrinology·W Q Zhao, D L Alkon
May 9, 2002·Behavioural Brain Research·Robert M J DeaconJ Nicholas P Rawlins
Aug 15, 2002·Pharmacology, Biochemistry, and Behavior·B E McKayN M Fournier
Mar 19, 2003·Behavioural Brain Research·Robert M J DeaconJ Nicholas P Rawlins
Jun 25, 2003·Neurology·G S WatsonS Craft
Feb 26, 2004·Lancet Neurology·Suzanne Craft, G Stennis Watson
Oct 16, 2004·Science·Umut OzcanGökhan S Hotamisligil
Sep 24, 2005·The Journal of Biological Chemistry·Buffie Clodfelder-MillerRichard S Jope
Mar 29, 2006·Cellular and Molecular Life Sciences : CMLS·Y BalaramanS Srinivasan
Dec 29, 2006·Diabetes Care·UNKNOWN American Diabetes Association
Apr 5, 2007·Nature Protocols·Robert M J Deacon
Sep 18, 2008·International Journal of Obesity : Journal of the International Association for the Study of Obesity·A Marette
Feb 27, 2010·European Journal of Pharmacology·Asadollah ZarifkarMaryam Moosavi
Sep 16, 2010·Nature Reviews. Neurology·Catrina Sims-RobinsonEva L Feldman
Nov 26, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Lindsay M EdwardsKieran Clarke
Jan 27, 2011·European Journal of Pharmacology·Atsuo TaharaMasayuki Shibasaki
Aug 23, 2011·Diabetes Research and Clinical Practice·Jong Hoon LeeJun Hyung Park
Oct 14, 2011·Journal of Neurosurgical Anesthesiology·Huisong CuiJong Eun Lee
Jan 17, 2012·Trends in Endocrinology and Metabolism : TEM·Bhumsoo Kim, Eva L Feldman
Feb 4, 2012·Progress in Neuro-psychopharmacology & Biological Psychiatry·Pravinkumar BhutadaKishor Jain
Feb 15, 2012·Current Alzheimer Research·Suzanne M de la Monte
Jun 12, 2012·Lancet·Adam G TabákMika Kivimäki
Jun 19, 2013·Drug Discovery Today·John E PiletzGad M Gilad
Sep 7, 2013·Diabetes Care·Eileen M MooreUNKNOWN AIBL Investigators

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Citations

Mar 24, 2017·Yonsei Medical Journal·Somang KangJong Eun Lee
Feb 16, 2019·Expert Opinion on Therapeutic Targets·Devon WattsFlavio Kapczinski
Jul 1, 2020·Fundamental & Clinical Pharmacology·Adel A GomaaMariam A Nicola
Jul 28, 2017·The Biochemical Journal·Gregor Laube, Hans-Gert Bernstein
Jul 6, 2019·Frontiers in Neuroscience·Sami GabboujTeemu Natunen
Feb 23, 2020·Journal of Diabetes Research·Yanan SunXu He
Aug 30, 2019·International Journal of Molecular Sciences·Hee Jae Lee, Soo Jin Yang
Dec 11, 2019·Drug Development Research·Kavya JashKiran Kalia
Jun 20, 2020·Annals of Neurology·Zoe ArvanitakisSteven E Arnold
Sep 29, 2020·Metabolic Brain Disease·Viplav KshirsagarArchana Juvekar
Oct 18, 2020·Nature Reviews. Neuroscience·Brittany D NeedhamSarkis K Mazmanian
Oct 23, 2020·The International Journal of Neuroscience·Sachin P BorikarKishor R Danao
Jan 8, 2021·Frontiers in Neuroscience·Chao-Chao YuLi-Hong Kong
Jan 18, 2018·Neurobiology of Aging·Hugo GirardUNKNOWN Alzheimer's Disease Neuroimaging Initiative
Jun 16, 2021·European Journal of Pharmacology·Nandkishor KotagaleBrijesh Taksande

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