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J Cell Biochem ; 119(7): 5657-5664, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29384214

RESUMO

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 (Aß) 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 Aß 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.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Insulina/farmacologia , Transcriptoma/efeitos dos fármacos , Transportadores de Cassetes de Ligação de ATP/genética , Peptídeos beta-Amiloides/metabolismo , Transporte Biológico , Barreira Hematoencefálica/efeitos dos fármacos , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Células Cultivadas , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Regulação da Expressão Gênica , Humanos , Hipoglicemiantes/farmacologia , Técnicas In Vitro , Modelos Biológicos
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