Effects of apolipoprotein E isoform, sex, and diet on insulin BBB pharmacokinetics in mice

Abstract Age, apolipoprotein E (apoE) isoform, sex, and diet can independently affect the risk for the development of Alzheimer’s disease (AD). Additionally, synergy between some of these risk factors have been observed. However, the relation between the latter three risk factors has not been invest...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Elizabeth M. Rhea, Kim Hansen, Sarah Pemberton, Eileen Ruth S. Torres, Sarah Holden, Jacob Raber, William A. Banks
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0ce3c93e82204b878b9431bc55726dc8
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:0ce3c93e82204b878b9431bc55726dc8
record_format	dspace
spelling	oai:doaj.org-article:0ce3c93e82204b878b9431bc55726dc82021-12-02T18:14:16ZEffects of apolipoprotein E isoform, sex, and diet on insulin BBB pharmacokinetics in mice10.1038/s41598-021-98061-12045-2322https://doaj.org/article/0ce3c93e82204b878b9431bc55726dc82021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98061-1https://doaj.org/toc/2045-2322Abstract Age, apolipoprotein E (apoE) isoform, sex, and diet can independently affect the risk for the development of Alzheimer’s disease (AD). Additionally, synergy between some of these risk factors have been observed. However, the relation between the latter three risk factors has not been investigated. Central nervous system (CNS) insulin resistance is commonly involved in each of these risk factors. CNS insulin is primarily derived from the periphery in which insulin must be transported across the blood–brain barrier (BBB). Additionally, insulin can bind the brain endothelial cell to affect intracellular signaling. Therefore, we hypothesized CNS access to insulin could be affected by the combination of apoE isoform, sex, and diet. We analyzed insulin BBB pharmacokinetics in aged apoE targeted replacement (E3 and E4) male and female mice on a low-fat and high-fat diet. There were differences within males and females due to apoE genotype and diet in insulin interactions at the BBB. These sex-, diet-, and apoE isoform-dependent differences could contribute to the cognitive changes observed due to altered CNS insulin signaling.Elizabeth M. RheaKim HansenSarah PembertonEileen Ruth S. TorresSarah HoldenJacob RaberWilliam A. BanksNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elizabeth M. Rhea Kim Hansen Sarah Pemberton Eileen Ruth S. Torres Sarah Holden Jacob Raber William A. Banks Effects of apolipoprotein E isoform, sex, and diet on insulin BBB pharmacokinetics in mice
description	Abstract Age, apolipoprotein E (apoE) isoform, sex, and diet can independently affect the risk for the development of Alzheimer’s disease (AD). Additionally, synergy between some of these risk factors have been observed. However, the relation between the latter three risk factors has not been investigated. Central nervous system (CNS) insulin resistance is commonly involved in each of these risk factors. CNS insulin is primarily derived from the periphery in which insulin must be transported across the blood–brain barrier (BBB). Additionally, insulin can bind the brain endothelial cell to affect intracellular signaling. Therefore, we hypothesized CNS access to insulin could be affected by the combination of apoE isoform, sex, and diet. We analyzed insulin BBB pharmacokinetics in aged apoE targeted replacement (E3 and E4) male and female mice on a low-fat and high-fat diet. There were differences within males and females due to apoE genotype and diet in insulin interactions at the BBB. These sex-, diet-, and apoE isoform-dependent differences could contribute to the cognitive changes observed due to altered CNS insulin signaling.
format	article
author	Elizabeth M. Rhea Kim Hansen Sarah Pemberton Eileen Ruth S. Torres Sarah Holden Jacob Raber William A. Banks
author_facet	Elizabeth M. Rhea Kim Hansen Sarah Pemberton Eileen Ruth S. Torres Sarah Holden Jacob Raber William A. Banks
author_sort	Elizabeth M. Rhea
title	Effects of apolipoprotein E isoform, sex, and diet on insulin BBB pharmacokinetics in mice
title_short	Effects of apolipoprotein E isoform, sex, and diet on insulin BBB pharmacokinetics in mice
title_full	Effects of apolipoprotein E isoform, sex, and diet on insulin BBB pharmacokinetics in mice
title_fullStr	Effects of apolipoprotein E isoform, sex, and diet on insulin BBB pharmacokinetics in mice
title_full_unstemmed	Effects of apolipoprotein E isoform, sex, and diet on insulin BBB pharmacokinetics in mice
title_sort	effects of apolipoprotein e isoform, sex, and diet on insulin bbb pharmacokinetics in mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0ce3c93e82204b878b9431bc55726dc8
work_keys_str_mv	AT elizabethmrhea effectsofapolipoproteineisoformsexanddietoninsulinbbbpharmacokineticsinmice AT kimhansen effectsofapolipoproteineisoformsexanddietoninsulinbbbpharmacokineticsinmice AT sarahpemberton effectsofapolipoproteineisoformsexanddietoninsulinbbbpharmacokineticsinmice AT eileenruthstorres effectsofapolipoproteineisoformsexanddietoninsulinbbbpharmacokineticsinmice AT sarahholden effectsofapolipoproteineisoformsexanddietoninsulinbbbpharmacokineticsinmice AT jacobraber effectsofapolipoproteineisoformsexanddietoninsulinbbbpharmacokineticsinmice AT williamabanks effectsofapolipoproteineisoformsexanddietoninsulinbbbpharmacokineticsinmice
_version_	1718378375541686272

Effects of apolipoprotein E isoform, sex, and diet on insulin BBB pharmacokinetics in mice

Ejemplares similares