Journal
JOURNAL OF CELLULAR BIOCHEMISTRY
Volume 119, Issue 7, Pages 5657-5664Publisher
WILEY
DOI: 10.1002/jcb.26744
Keywords
Alzheimer's disease; human blood-brain barrier; insulin; type 2 diabetes; transcriptional response; permeability
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Funding
- Industrial Technology Research and Development Projects of Jilin Province Development and Reform Commission [2014Y081]
- National Natural Science Foundation of China [31770996]
- Science and Technology Enterprise Technology Innovation Fund by Jiangsu Province Science and Technology Department [BC2015065]
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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 (A) 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 A 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.
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