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Circadian Clock Component BMAL1 in the Paraventricular Nucleus Regulates Glucose Metabolism
It is suggested that clock genes link the circadian rhythm to glucose and lipid metabolism. In this study, we explored the role of the clock gene Bmal1 in the hypothalamic paraventricular nucleus (PVN) in glucose metabolism. The Sim1-Cre-mediated deletion of Bmal1 markedly reduced insulin secretion,...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8707417/ https://www.ncbi.nlm.nih.gov/pubmed/34960038 http://dx.doi.org/10.3390/nu13124487 |
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author | Nakata, Masanori Kumari, Parmila Kita, Rika Katsui, Nanako Takeuchi, Yuriko Kawaguchi, Tomoki Yamazaki, Toshiya Zhang, Boyang Shimba, Shigeki Yada, Toshihiko |
author_facet | Nakata, Masanori Kumari, Parmila Kita, Rika Katsui, Nanako Takeuchi, Yuriko Kawaguchi, Tomoki Yamazaki, Toshiya Zhang, Boyang Shimba, Shigeki Yada, Toshihiko |
author_sort | Nakata, Masanori |
collection | PubMed |
description | It is suggested that clock genes link the circadian rhythm to glucose and lipid metabolism. In this study, we explored the role of the clock gene Bmal1 in the hypothalamic paraventricular nucleus (PVN) in glucose metabolism. The Sim1-Cre-mediated deletion of Bmal1 markedly reduced insulin secretion, resulting in impaired glucose tolerance. The pancreatic islets’ responses to glucose, sulfonylureas (SUs) and arginine vasopressin (AVP) were well maintained. To specify the PVN neuron subpopulation targeted by Bmal1, the expression of neuropeptides was examined. In these knockout (KO) mice, the mRNA expression of Avp in the PVN was selectively decreased, and the plasma AVP concentration was also decreased. However, fasting suppressed Avp expression in both KO and Cre mice. These results demonstrate that PVN BMAL1 maintains Avp expression in the PVN and release to the circulation, possibly providing islet β-cells with more AVP. This action helps enhance insulin release and, consequently, glucose tolerance. In contrast, the circadian variation of Avp expression is regulated by feeding, but not by PVN BMAL1. |
format | Online Article Text |
id | pubmed-8707417 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87074172021-12-25 Circadian Clock Component BMAL1 in the Paraventricular Nucleus Regulates Glucose Metabolism Nakata, Masanori Kumari, Parmila Kita, Rika Katsui, Nanako Takeuchi, Yuriko Kawaguchi, Tomoki Yamazaki, Toshiya Zhang, Boyang Shimba, Shigeki Yada, Toshihiko Nutrients Article It is suggested that clock genes link the circadian rhythm to glucose and lipid metabolism. In this study, we explored the role of the clock gene Bmal1 in the hypothalamic paraventricular nucleus (PVN) in glucose metabolism. The Sim1-Cre-mediated deletion of Bmal1 markedly reduced insulin secretion, resulting in impaired glucose tolerance. The pancreatic islets’ responses to glucose, sulfonylureas (SUs) and arginine vasopressin (AVP) were well maintained. To specify the PVN neuron subpopulation targeted by Bmal1, the expression of neuropeptides was examined. In these knockout (KO) mice, the mRNA expression of Avp in the PVN was selectively decreased, and the plasma AVP concentration was also decreased. However, fasting suppressed Avp expression in both KO and Cre mice. These results demonstrate that PVN BMAL1 maintains Avp expression in the PVN and release to the circulation, possibly providing islet β-cells with more AVP. This action helps enhance insulin release and, consequently, glucose tolerance. In contrast, the circadian variation of Avp expression is regulated by feeding, but not by PVN BMAL1. MDPI 2021-12-15 /pmc/articles/PMC8707417/ /pubmed/34960038 http://dx.doi.org/10.3390/nu13124487 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Nakata, Masanori Kumari, Parmila Kita, Rika Katsui, Nanako Takeuchi, Yuriko Kawaguchi, Tomoki Yamazaki, Toshiya Zhang, Boyang Shimba, Shigeki Yada, Toshihiko Circadian Clock Component BMAL1 in the Paraventricular Nucleus Regulates Glucose Metabolism |
title | Circadian Clock Component BMAL1 in the Paraventricular Nucleus Regulates Glucose Metabolism |
title_full | Circadian Clock Component BMAL1 in the Paraventricular Nucleus Regulates Glucose Metabolism |
title_fullStr | Circadian Clock Component BMAL1 in the Paraventricular Nucleus Regulates Glucose Metabolism |
title_full_unstemmed | Circadian Clock Component BMAL1 in the Paraventricular Nucleus Regulates Glucose Metabolism |
title_short | Circadian Clock Component BMAL1 in the Paraventricular Nucleus Regulates Glucose Metabolism |
title_sort | circadian clock component bmal1 in the paraventricular nucleus regulates glucose metabolism |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8707417/ https://www.ncbi.nlm.nih.gov/pubmed/34960038 http://dx.doi.org/10.3390/nu13124487 |
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