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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
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.
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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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