The effects of agmatine on Alzheimer's disease induced by brain insulin resistance

Abstract

Type 2 diabetes increases risk of Alzheimer’s disease, especially neuronal insulin resistance is suggested as a main cause of Alzheimer’s disease occurred in type 2 diabetes patients. Reduced insulin signaling in neurons leads to neuronal dysfunction, accumulation of amyloid beta (Aβ) and phosphorylation of tau. Agmatine, a polyamine derived from L-arginine, has shown neuroprotective effects. This study was designed to investigate whether agmatine could reduce both high fat diet induced peripheral glucose intolerance and cognitive impairment through retrieval blunted insulin signaling in brain. 8 weeks old male ICR mice weighing 30~35 g were randomly divided into 2 groups and fed normal diet and 60% high fat diet for 12 weeks. High fat diet group was injected streptozotocin (100 mg/kg/ip) once at 4th weeks of diet. After 12 weeks, mice in high fat diet group were assigned into 2 groups, saline or agmatine (100 mg/kg/ip) treated groups. After 2 weeks of treatment, behavior tests were conducted and brains were collected for western blotting and immunohistochemistry. Expression levels of insulin downstream molecules, Aβ and phosphorylated tau were evaluated. Agmatine administration relieved peripheral glucose intolerance and reduced accumulation of Aβ and phosphorylated tau caused by high fat diet through retrieval of insulin signaling. Agmatine rescues high fat diet fed mice from cognitive decline as well. Agmatine may have potential to be a candidate substance for treat both diabetes and Alzheimer’s disease.