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Paraventricular Vitamin D Receptors Are Required for Glucose Tolerance in Males but Not Females

When delivered directly into the brain, vitamin D, can improve glucose levels in male mice. Additionally, the loss of the vitamin D receptor (VDR) in male mice’s paraventricular hypothalamus (PVH) results in impaired glucose tolerance. Data in humans shows that low vitamin D levels are detrimental t...

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Autores principales: Beck, Jessie, da Silva Teixeira, Silvania, Harrison, Keisha, Phillips, Gabrielle, He, Yanlin, Sisley, Stephanie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128386/
https://www.ncbi.nlm.nih.gov/pubmed/35620386
http://dx.doi.org/10.3389/fendo.2022.869678
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author Beck, Jessie
da Silva Teixeira, Silvania
Harrison, Keisha
Phillips, Gabrielle
He, Yanlin
Sisley, Stephanie
author_facet Beck, Jessie
da Silva Teixeira, Silvania
Harrison, Keisha
Phillips, Gabrielle
He, Yanlin
Sisley, Stephanie
author_sort Beck, Jessie
collection PubMed
description When delivered directly into the brain, vitamin D, can improve glucose levels in male mice. Additionally, the loss of the vitamin D receptor (VDR) in male mice’s paraventricular hypothalamus (PVH) results in impaired glucose tolerance. Data in humans shows that low vitamin D levels are detrimental to glucose homeostasis, an effect that may be more prominent in men. However, it is unknown if vitamin D action in the brain is required for normal glucose regulation in female mice. This study shows that in both viral and genetic models, male mice with obesity and PVH VDR loss have impaired glucose tolerance while female mice are unaffected. Weights were unaltered in both sexes by PVH VDR loss. Additionally, PVH VDR loss did not cause any glucose abnormalities in either sex when the mice were on a chow diet. Utilizing electrophysiology studies, we show PVH VDR loss resulted in decreased baseline firing frequency and resting membrane potential in males, but not females. Additionally, male mice with PVH VDR loss had impaired miniature excitatory postsynaptic currents (mEPSC), while females were unaffected. Interestingly, the PVH neurons of both sexes were activated by exogenous vitamin D (1,25-dihydroxyvitamin D3), an effect dependent upon the VDR. Thus, there is sexual dimorphism, for the actions of the PVH VDR on glucose regulation. PVH VDRs are necessary for normal glucose homeostasis in males but not females and this may be secondary to actions of the VDR on neuronal activity.
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spelling pubmed-91283862022-05-25 Paraventricular Vitamin D Receptors Are Required for Glucose Tolerance in Males but Not Females Beck, Jessie da Silva Teixeira, Silvania Harrison, Keisha Phillips, Gabrielle He, Yanlin Sisley, Stephanie Front Endocrinol (Lausanne) Endocrinology When delivered directly into the brain, vitamin D, can improve glucose levels in male mice. Additionally, the loss of the vitamin D receptor (VDR) in male mice’s paraventricular hypothalamus (PVH) results in impaired glucose tolerance. Data in humans shows that low vitamin D levels are detrimental to glucose homeostasis, an effect that may be more prominent in men. However, it is unknown if vitamin D action in the brain is required for normal glucose regulation in female mice. This study shows that in both viral and genetic models, male mice with obesity and PVH VDR loss have impaired glucose tolerance while female mice are unaffected. Weights were unaltered in both sexes by PVH VDR loss. Additionally, PVH VDR loss did not cause any glucose abnormalities in either sex when the mice were on a chow diet. Utilizing electrophysiology studies, we show PVH VDR loss resulted in decreased baseline firing frequency and resting membrane potential in males, but not females. Additionally, male mice with PVH VDR loss had impaired miniature excitatory postsynaptic currents (mEPSC), while females were unaffected. Interestingly, the PVH neurons of both sexes were activated by exogenous vitamin D (1,25-dihydroxyvitamin D3), an effect dependent upon the VDR. Thus, there is sexual dimorphism, for the actions of the PVH VDR on glucose regulation. PVH VDRs are necessary for normal glucose homeostasis in males but not females and this may be secondary to actions of the VDR on neuronal activity. Frontiers Media S.A. 2022-05-10 /pmc/articles/PMC9128386/ /pubmed/35620386 http://dx.doi.org/10.3389/fendo.2022.869678 Text en Copyright © 2022 Beck, da Silva Teixeira, Harrison, Phillips, He and Sisley https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Beck, Jessie
da Silva Teixeira, Silvania
Harrison, Keisha
Phillips, Gabrielle
He, Yanlin
Sisley, Stephanie
Paraventricular Vitamin D Receptors Are Required for Glucose Tolerance in Males but Not Females
title Paraventricular Vitamin D Receptors Are Required for Glucose Tolerance in Males but Not Females
title_full Paraventricular Vitamin D Receptors Are Required for Glucose Tolerance in Males but Not Females
title_fullStr Paraventricular Vitamin D Receptors Are Required for Glucose Tolerance in Males but Not Females
title_full_unstemmed Paraventricular Vitamin D Receptors Are Required for Glucose Tolerance in Males but Not Females
title_short Paraventricular Vitamin D Receptors Are Required for Glucose Tolerance in Males but Not Females
title_sort paraventricular vitamin d receptors are required for glucose tolerance in males but not females
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128386/
https://www.ncbi.nlm.nih.gov/pubmed/35620386
http://dx.doi.org/10.3389/fendo.2022.869678
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