Cargando…

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,...

Descripción completa

Detalles Bibliográficos
Autores principales: Nakata, Masanori, Kumari, Parmila, Kita, Rika, Katsui, Nanako, Takeuchi, Yuriko, Kawaguchi, Tomoki, Yamazaki, Toshiya, Zhang, Boyang, Shimba, Shigeki, Yada, Toshihiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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
_version_ 1784622431818743808
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
work_keys_str_mv AT nakatamasanori circadianclockcomponentbmal1intheparaventricularnucleusregulatesglucosemetabolism
AT kumariparmila circadianclockcomponentbmal1intheparaventricularnucleusregulatesglucosemetabolism
AT kitarika circadianclockcomponentbmal1intheparaventricularnucleusregulatesglucosemetabolism
AT katsuinanako circadianclockcomponentbmal1intheparaventricularnucleusregulatesglucosemetabolism
AT takeuchiyuriko circadianclockcomponentbmal1intheparaventricularnucleusregulatesglucosemetabolism
AT kawaguchitomoki circadianclockcomponentbmal1intheparaventricularnucleusregulatesglucosemetabolism
AT yamazakitoshiya circadianclockcomponentbmal1intheparaventricularnucleusregulatesglucosemetabolism
AT zhangboyang circadianclockcomponentbmal1intheparaventricularnucleusregulatesglucosemetabolism
AT shimbashigeki circadianclockcomponentbmal1intheparaventricularnucleusregulatesglucosemetabolism
AT yadatoshihiko circadianclockcomponentbmal1intheparaventricularnucleusregulatesglucosemetabolism