Cargando…
Neuronal signals regulate obesity induced β-cell proliferation by FoxM1 dependent mechanism
Under insulin-resistant conditions such as obesity, pancreatic β-cells proliferate to prevent blood glucose elevations. A liver–brain–pancreas neuronal relay plays an important role in this process. Here, we show the molecular mechanism underlying this compensatory β-cell proliferation. We identify...
Autores principales: | , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717276/ https://www.ncbi.nlm.nih.gov/pubmed/29208957 http://dx.doi.org/10.1038/s41467-017-01869-7 |
_version_ | 1783284110770307072 |
---|---|
author | Yamamoto, Junpei Imai, Junta Izumi, Tomohito Takahashi, Hironori Kawana, Yohei Takahashi, Kei Kodama, Shinjiro Kaneko, Keizo Gao, Junhong Uno, Kenji Sawada, Shojiro Asano, Tomoichiro Kalinichenko, Vladimir V. Susaki, Etsuo A. Kanzaki, Makoto Ueda, Hiroki R. Ishigaki, Yasushi Yamada, Tetsuya Katagiri, Hideki |
author_facet | Yamamoto, Junpei Imai, Junta Izumi, Tomohito Takahashi, Hironori Kawana, Yohei Takahashi, Kei Kodama, Shinjiro Kaneko, Keizo Gao, Junhong Uno, Kenji Sawada, Shojiro Asano, Tomoichiro Kalinichenko, Vladimir V. Susaki, Etsuo A. Kanzaki, Makoto Ueda, Hiroki R. Ishigaki, Yasushi Yamada, Tetsuya Katagiri, Hideki |
author_sort | Yamamoto, Junpei |
collection | PubMed |
description | Under insulin-resistant conditions such as obesity, pancreatic β-cells proliferate to prevent blood glucose elevations. A liver–brain–pancreas neuronal relay plays an important role in this process. Here, we show the molecular mechanism underlying this compensatory β-cell proliferation. We identify FoxM1 activation in islets from neuronal relay-stimulated mice. Blockade of this relay, including vagotomy, inhibits obesity-induced activation of the β-cell FoxM1 pathway and suppresses β-cell expansion. Inducible β-cell-specific FoxM1 deficiency also blocks compensatory β-cell proliferation. In isolated islets, carbachol and PACAP/VIP synergistically promote β-cell proliferation through a FoxM1-dependent mechanism. These findings indicate that vagal nerves that release several neurotransmitters may allow simultaneous activation of multiple pathways in β-cells selectively, thereby efficiently promoting β-cell proliferation and maintaining glucose homeostasis during obesity development. This neuronal signal-mediated mechanism holds potential for developing novel approaches to regenerating pancreatic β-cells. |
format | Online Article Text |
id | pubmed-5717276 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-57172762017-12-08 Neuronal signals regulate obesity induced β-cell proliferation by FoxM1 dependent mechanism Yamamoto, Junpei Imai, Junta Izumi, Tomohito Takahashi, Hironori Kawana, Yohei Takahashi, Kei Kodama, Shinjiro Kaneko, Keizo Gao, Junhong Uno, Kenji Sawada, Shojiro Asano, Tomoichiro Kalinichenko, Vladimir V. Susaki, Etsuo A. Kanzaki, Makoto Ueda, Hiroki R. Ishigaki, Yasushi Yamada, Tetsuya Katagiri, Hideki Nat Commun Article Under insulin-resistant conditions such as obesity, pancreatic β-cells proliferate to prevent blood glucose elevations. A liver–brain–pancreas neuronal relay plays an important role in this process. Here, we show the molecular mechanism underlying this compensatory β-cell proliferation. We identify FoxM1 activation in islets from neuronal relay-stimulated mice. Blockade of this relay, including vagotomy, inhibits obesity-induced activation of the β-cell FoxM1 pathway and suppresses β-cell expansion. Inducible β-cell-specific FoxM1 deficiency also blocks compensatory β-cell proliferation. In isolated islets, carbachol and PACAP/VIP synergistically promote β-cell proliferation through a FoxM1-dependent mechanism. These findings indicate that vagal nerves that release several neurotransmitters may allow simultaneous activation of multiple pathways in β-cells selectively, thereby efficiently promoting β-cell proliferation and maintaining glucose homeostasis during obesity development. This neuronal signal-mediated mechanism holds potential for developing novel approaches to regenerating pancreatic β-cells. Nature Publishing Group UK 2017-12-05 /pmc/articles/PMC5717276/ /pubmed/29208957 http://dx.doi.org/10.1038/s41467-017-01869-7 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Yamamoto, Junpei Imai, Junta Izumi, Tomohito Takahashi, Hironori Kawana, Yohei Takahashi, Kei Kodama, Shinjiro Kaneko, Keizo Gao, Junhong Uno, Kenji Sawada, Shojiro Asano, Tomoichiro Kalinichenko, Vladimir V. Susaki, Etsuo A. Kanzaki, Makoto Ueda, Hiroki R. Ishigaki, Yasushi Yamada, Tetsuya Katagiri, Hideki Neuronal signals regulate obesity induced β-cell proliferation by FoxM1 dependent mechanism |
title | Neuronal signals regulate obesity induced β-cell proliferation by FoxM1 dependent mechanism |
title_full | Neuronal signals regulate obesity induced β-cell proliferation by FoxM1 dependent mechanism |
title_fullStr | Neuronal signals regulate obesity induced β-cell proliferation by FoxM1 dependent mechanism |
title_full_unstemmed | Neuronal signals regulate obesity induced β-cell proliferation by FoxM1 dependent mechanism |
title_short | Neuronal signals regulate obesity induced β-cell proliferation by FoxM1 dependent mechanism |
title_sort | neuronal signals regulate obesity induced β-cell proliferation by foxm1 dependent mechanism |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717276/ https://www.ncbi.nlm.nih.gov/pubmed/29208957 http://dx.doi.org/10.1038/s41467-017-01869-7 |
work_keys_str_mv | AT yamamotojunpei neuronalsignalsregulateobesityinducedbcellproliferationbyfoxm1dependentmechanism AT imaijunta neuronalsignalsregulateobesityinducedbcellproliferationbyfoxm1dependentmechanism AT izumitomohito neuronalsignalsregulateobesityinducedbcellproliferationbyfoxm1dependentmechanism AT takahashihironori neuronalsignalsregulateobesityinducedbcellproliferationbyfoxm1dependentmechanism AT kawanayohei neuronalsignalsregulateobesityinducedbcellproliferationbyfoxm1dependentmechanism AT takahashikei neuronalsignalsregulateobesityinducedbcellproliferationbyfoxm1dependentmechanism AT kodamashinjiro neuronalsignalsregulateobesityinducedbcellproliferationbyfoxm1dependentmechanism AT kanekokeizo neuronalsignalsregulateobesityinducedbcellproliferationbyfoxm1dependentmechanism AT gaojunhong neuronalsignalsregulateobesityinducedbcellproliferationbyfoxm1dependentmechanism AT unokenji neuronalsignalsregulateobesityinducedbcellproliferationbyfoxm1dependentmechanism AT sawadashojiro neuronalsignalsregulateobesityinducedbcellproliferationbyfoxm1dependentmechanism AT asanotomoichiro neuronalsignalsregulateobesityinducedbcellproliferationbyfoxm1dependentmechanism AT kalinichenkovladimirv neuronalsignalsregulateobesityinducedbcellproliferationbyfoxm1dependentmechanism AT susakietsuoa neuronalsignalsregulateobesityinducedbcellproliferationbyfoxm1dependentmechanism AT kanzakimakoto neuronalsignalsregulateobesityinducedbcellproliferationbyfoxm1dependentmechanism AT uedahirokir neuronalsignalsregulateobesityinducedbcellproliferationbyfoxm1dependentmechanism AT ishigakiyasushi neuronalsignalsregulateobesityinducedbcellproliferationbyfoxm1dependentmechanism AT yamadatetsuya neuronalsignalsregulateobesityinducedbcellproliferationbyfoxm1dependentmechanism AT katagirihideki neuronalsignalsregulateobesityinducedbcellproliferationbyfoxm1dependentmechanism |