Effects of insulin on transcriptional response and permeability in an in vitro model of human blood‐brain barrier. Issue 7 (12th March 2018)

• Record Type: Journal Article
• Authors: Kuai, Ziyu; Xu, Yan; Zhao, Qi; Liu, Jie; Guan, Shanshan; Qiao, Yongbo; Gong, Xin; Nie, Jiaojiao; Li, Pengju; Liu, Dongni; Xing, Yifan; Li, Huiwen; Sun, Zixiao; Wang, Wenqi; Ning, Chunan; Shi, Yuhua; Kong, Wei; Shan, Yaming
• Is Part Of: Journal of cellular biochemistry. Volume 119:Issue 7(2018)
• Page Start: 5657
• Page End: 5664
• Publication Date: 2018-03-12
• Subjects: Alzheimer's disease -- human blood‐brain barrier -- insulin -- type 2 diabetes -- transcriptional response -- permeability; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.26744
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Alzheimer's disease (AD) is the most prevalent form of dementia worldwide and is an emerging global epidemic. Active and passive immune therapies targeting beta amyloid (Aβ) have shown very limited evidence in human studies of clinical benefits from these approaches. Epidemiological studies have shown that subjects with type 2 diabetes (T2D) are at higher risk of developing AD. However, whether and how these two conditions are causally linked is unknown. With the purpose of confirming the relationship between T2D and AD, this study specifically focused on effects of insulin in an in vitro model of the human blood‐brain barrier (BBB) and on potential mechanisms of action in the treatment of AD. By using a series of assays to establish a BBB model, we demonstrated that insulin treatment alone could induce the increase of brain endothelial barrier properties. The transcriptional response of hCMEC/D3 cells to activation with different concentrations of insulin was determined by RT‐PCR, and expression levels of genes involved in the control of barrier permeability, including inter‐brain endothelial junctions, integrin‐focal adhesions complexes, and transporter system, were found to be altered by the treatment. Notably, the influence of insulin on expression of the ATP‐binding cassette (ABC) transporter which contributes to the clearance of Aβ was investigated. Insulin up‐regulated adherens junction and tight junction transmembrane proteins, as well as the ABC transporter. By treatment with insulin, the models have major advantages: it is fast, it has low cost, it is fit for considerable samples, and its conditions are under control. Abstract : Insulin may affect brain Aβ clearance by modulatinginhibition of the Aβ influx by permeability factors junctional protein: CDH5 and ANXA2, cell‐to‐matrix contacts: ITGB1 and FHL or efflux transporters such as ABC transporter. Insulin in the brain may also increase Aβ drainage to the cerebrospinal fluid (CSF) and/or reduce Aβ production.