TY - JOUR
T1 - Effects of apolipoprotein E isoform, sex, and diet on insulin BBB pharmacokinetics in mice
AU - Rhea, Elizabeth M.
AU - Hansen, Kim
AU - Pemberton, Sarah
AU - Torres, Eileen Ruth S.
AU - Holden, Sarah
AU - Raber, Jacob
AU - Banks, William A.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-021-98061-1
DO - 10.1038/s41598-021-98061-1
M3 - Article
C2 - 34545146
AN - SCOPUS:85115398840
SN - 2045-2322
VL - 11
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 18636
ER -