High glucose exacerbates β-amyloid production and the beneficial role of benfotiamine in vitro
会议名称：《中国神经科学学会第九届全国学术会议暨第五次会员代表大会》
会议日期：2011年
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
关 键 词：Alzheimer’s disease diabetes mellitus benfotiamene glycogen synthase kinase-3
摘 要：正Our previous study has demonstrated that benfotiamine,a protective agent for diabetes complications, significantly decreases p-amyloid（Aβ） production through enhancing the phosphorylation levels and reduced enzymatic activities of both GSK-3αand GSK-3βin the APP/PS1 transgenic *** evidence from a population- based study also shows a link between Alzheimer’s disease（AD） and diabetes mellitus（DM）.The prevelance rate of AD is high as much as 2 to 5 times in population suffering from DM compared with non-DM control subjects. Experimental investigations suggest that the abnormality of cerebral glucose metabolism is the key etiological factor for *** we explored the effect of benfotiamine on high glucose exacerbating Aβproduction and the possible mechanism using HEK293 APPsw overexpression *** results showed that Aβproduction was first rising and then dropping along with the increased concentrations of glucose in the cell culture medium（1 g/L,3 g/L,4.5 g/ L,5.5 g/L,6.5 g/L,7.5 g/L,8.5 g/L,10.5 g/L） and the prolongation of incubated time（6,12,and 24 h）.After being incubated for 6 h or 12 h,the Aβproduction of cells incubated in 5.5 g/L glucose was higher significantly compared with those of cells in 1 g/L glucose（6 h,P0.05;12 h,P0.01）.It was associated with high glucose up-regulating the activities of GSK-3:The ratios of p-GSK-3a/GSK-3a and p-GSK-3β/GSK-3βin 5.5 g/L group were significantly decreased（p-GSK-3α/GSK-3α,P0.01;p-GSK-3β/GSK-3β,P0.05）,and the activities of GSK-3a and GSK- 3βwere significantly increased compared with those in 1.0 g/L group（P0.05）.Benfotiamine significantly reduced Aβproduction enhanced by high glucose compared with control group（20 ug/mL group P0.05,40μg/mL group P0.01）.The mechanisms may be through modulating GSK-3 activities:Benfotiamine（40μg/mL） significantly decreased the activities of GSK-3a and GSK-3βcompared with control group（P0.05）.Increased Aβproduction induced by high glucose is associated with the up-regula