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...
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2021-09-01
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doaj-0ce3c93e82204b878b9431bc55726dc82021-09-26T11:29:05ZengNature Publishing GroupScientific Reports2045-23222021-09-0111111110.1038/s41598-021-98061-1Effects of apolipoprotein E isoform, sex, and diet on insulin BBB pharmacokinetics in miceElizabeth M. Rhea0Kim Hansen1Sarah Pemberton2Eileen Ruth S. Torres3Sarah Holden4Jacob Raber5William A. Banks6Department of Medicine, Division of Gerontology and Geriatric Medicine, University of WashingtonGeriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care SystemGeriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care SystemDepartment of Behavioral Neuroscience, Oregon Health & Science UniversityDepartment of Behavioral Neuroscience, Oregon Health & Science UniversityDepartment of Behavioral Neuroscience, Oregon Health & Science UniversityDepartment of Medicine, Division of Gerontology and Geriatric Medicine, University of WashingtonAbstract 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.https://doi.org/10.1038/s41598-021-98061-1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Elizabeth M. Rhea Kim Hansen Sarah Pemberton Eileen Ruth S. Torres Sarah Holden Jacob Raber William A. Banks |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-09-01 |
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. |
url |
https://doi.org/10.1038/s41598-021-98061-1 |
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