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Histidine Augments the Suppression of Hepatic Glucose Production by Central Insulin Action
Glucose intolerance in type 2 diabetes is related to enhanced hepatic glucose production (HGP) due to the increased expression of hepatic gluconeogenic enzymes. Previously, we revealed that hepatic STAT3 decreases the expression of hepatic gluconeogenic enzymes and suppresses HGP. Here, we show that...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712067/ https://www.ncbi.nlm.nih.gov/pubmed/23474485 http://dx.doi.org/10.2337/db12-1701 |
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author | Kimura, Kumi Nakamura, Yusuke Inaba, Yuka Matsumoto, Michihiro Kido, Yoshiaki Asahara, Shun-ichiro Matsuda, Tomokazu Watanabe, Hiroshi Maeda, Akifumi Inagaki, Fuyuhiko Mukai, Chisato Takeda, Kiyoshi Akira, Shizuo Ota, Tsuguhito Nakabayashi, Hajime Kaneko, Shuichi Kasuga, Masato Inoue, Hiroshi |
author_facet | Kimura, Kumi Nakamura, Yusuke Inaba, Yuka Matsumoto, Michihiro Kido, Yoshiaki Asahara, Shun-ichiro Matsuda, Tomokazu Watanabe, Hiroshi Maeda, Akifumi Inagaki, Fuyuhiko Mukai, Chisato Takeda, Kiyoshi Akira, Shizuo Ota, Tsuguhito Nakabayashi, Hajime Kaneko, Shuichi Kasuga, Masato Inoue, Hiroshi |
author_sort | Kimura, Kumi |
collection | PubMed |
description | Glucose intolerance in type 2 diabetes is related to enhanced hepatic glucose production (HGP) due to the increased expression of hepatic gluconeogenic enzymes. Previously, we revealed that hepatic STAT3 decreases the expression of hepatic gluconeogenic enzymes and suppresses HGP. Here, we show that increased plasma histidine results in hepatic STAT3 activation. Intravenous and intracerebroventricular (ICV) administration of histidine-activated hepatic STAT3 reduced G6Pase protein and mRNA levels and augmented HGP suppression by insulin. This suppression of hepatic gluconeogenesis by histidine was abolished by hepatic STAT3 deficiency or hepatic Kupffer cell depletion. Inhibition of HGP by histidine was also blocked by ICV administration of a histamine H(1) receptor antagonist. Therefore, histidine activates hepatic STAT3 and suppresses HGP via central histamine action. Hepatic STAT3 phosphorylation after histidine ICV administration was attenuated in histamine H(1) receptor knockout (Hrh1KO) mice but not in neuron-specific insulin receptor knockout (NIRKO) mice. Conversely, hepatic STAT3 phosphorylation after insulin ICV administration was attenuated in NIRKO but not in Hrh1KO mice. These findings suggest that central histidine action is independent of central insulin action, while both have additive effects on HGP suppression. Our results indicate that central histidine/histamine-mediated suppression of HGP is a potential target for the treatment of type 2 diabetes. |
format | Online Article Text |
id | pubmed-3712067 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-37120672014-07-01 Histidine Augments the Suppression of Hepatic Glucose Production by Central Insulin Action Kimura, Kumi Nakamura, Yusuke Inaba, Yuka Matsumoto, Michihiro Kido, Yoshiaki Asahara, Shun-ichiro Matsuda, Tomokazu Watanabe, Hiroshi Maeda, Akifumi Inagaki, Fuyuhiko Mukai, Chisato Takeda, Kiyoshi Akira, Shizuo Ota, Tsuguhito Nakabayashi, Hajime Kaneko, Shuichi Kasuga, Masato Inoue, Hiroshi Diabetes Original Research Glucose intolerance in type 2 diabetes is related to enhanced hepatic glucose production (HGP) due to the increased expression of hepatic gluconeogenic enzymes. Previously, we revealed that hepatic STAT3 decreases the expression of hepatic gluconeogenic enzymes and suppresses HGP. Here, we show that increased plasma histidine results in hepatic STAT3 activation. Intravenous and intracerebroventricular (ICV) administration of histidine-activated hepatic STAT3 reduced G6Pase protein and mRNA levels and augmented HGP suppression by insulin. This suppression of hepatic gluconeogenesis by histidine was abolished by hepatic STAT3 deficiency or hepatic Kupffer cell depletion. Inhibition of HGP by histidine was also blocked by ICV administration of a histamine H(1) receptor antagonist. Therefore, histidine activates hepatic STAT3 and suppresses HGP via central histamine action. Hepatic STAT3 phosphorylation after histidine ICV administration was attenuated in histamine H(1) receptor knockout (Hrh1KO) mice but not in neuron-specific insulin receptor knockout (NIRKO) mice. Conversely, hepatic STAT3 phosphorylation after insulin ICV administration was attenuated in NIRKO but not in Hrh1KO mice. These findings suggest that central histidine action is independent of central insulin action, while both have additive effects on HGP suppression. Our results indicate that central histidine/histamine-mediated suppression of HGP is a potential target for the treatment of type 2 diabetes. American Diabetes Association 2013-07 2013-06-14 /pmc/articles/PMC3712067/ /pubmed/23474485 http://dx.doi.org/10.2337/db12-1701 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Original Research Kimura, Kumi Nakamura, Yusuke Inaba, Yuka Matsumoto, Michihiro Kido, Yoshiaki Asahara, Shun-ichiro Matsuda, Tomokazu Watanabe, Hiroshi Maeda, Akifumi Inagaki, Fuyuhiko Mukai, Chisato Takeda, Kiyoshi Akira, Shizuo Ota, Tsuguhito Nakabayashi, Hajime Kaneko, Shuichi Kasuga, Masato Inoue, Hiroshi Histidine Augments the Suppression of Hepatic Glucose Production by Central Insulin Action |
title | Histidine Augments the Suppression of Hepatic Glucose Production by Central Insulin Action |
title_full | Histidine Augments the Suppression of Hepatic Glucose Production by Central Insulin Action |
title_fullStr | Histidine Augments the Suppression of Hepatic Glucose Production by Central Insulin Action |
title_full_unstemmed | Histidine Augments the Suppression of Hepatic Glucose Production by Central Insulin Action |
title_short | Histidine Augments the Suppression of Hepatic Glucose Production by Central Insulin Action |
title_sort | histidine augments the suppression of hepatic glucose production by central insulin action |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712067/ https://www.ncbi.nlm.nih.gov/pubmed/23474485 http://dx.doi.org/10.2337/db12-1701 |
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