Central dopamine D2 receptors regulate plasma glucose levels in mice through autonomic nerves

Abstract Recent evidence suggests that the central nervous system (CNS) regulates plasma glucose levels, but the underlying mechanism is unclear. The present study investigated the role of dopaminergic function in the CNS in regulation of plasma glucose levels in mice. I.c.v. injection of neither th...

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Autores principales:	Hiroko Ikeda, Naomi Yonemochi, Risa Mikami, Manabu Abe, Meiko Kawamura, Rie Natsume, Kenji Sakimura, John L. Waddington, Junzo Kamei
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/47ef45d4b1a8495a87b36e3b35248b64
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spelling	oai:doaj.org-article:47ef45d4b1a8495a87b36e3b35248b642021-12-02T13:58:12ZCentral dopamine D2 receptors regulate plasma glucose levels in mice through autonomic nerves10.1038/s41598-020-79292-02045-2322https://doaj.org/article/47ef45d4b1a8495a87b36e3b35248b642020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79292-0https://doaj.org/toc/2045-2322Abstract Recent evidence suggests that the central nervous system (CNS) regulates plasma glucose levels, but the underlying mechanism is unclear. The present study investigated the role of dopaminergic function in the CNS in regulation of plasma glucose levels in mice. I.c.v. injection of neither the dopamine D1 receptor agonist SKF 38393 nor the antagonist SCH 23390 influenced plasma glucose levels. In contrast, i.c.v. injection of both the dopamine D2 receptor agonist quinpirole and the antagonist l-sulpiride increased plasma glucose levels. Hyperglycemia induced by quinpirole and l-sulpiride was absent in dopamine D2 receptor knockout mice. I.c.v. injection of quinpirole and l-sulpiride each increased mRNA levels of hepatic glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, which are the key enzymes for hepatic gluconeogenesis. Systemic injection of the β2 adrenoceptor antagonist ICI 118,551 inhibited hyperglycemia induced by l-sulpiride, but not by quinpirole. In contrast, hyperglycemia induced by quinpirole, but not by l-sulpiride, was inhibited by hepatic vagotomy. These results suggest that stimulation of central dopamine D2 receptors increases plasma glucose level by increasing hepatic glucose production through parasympathetic nerves, whereas inhibition of central dopamine D2 receptors increases plasma glucose level by increasing hepatic glucose production through sympathetic nerves.Hiroko IkedaNaomi YonemochiRisa MikamiManabu AbeMeiko KawamuraRie NatsumeKenji SakimuraJohn L. WaddingtonJunzo KameiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-11 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hiroko Ikeda Naomi Yonemochi Risa Mikami Manabu Abe Meiko Kawamura Rie Natsume Kenji Sakimura John L. Waddington Junzo Kamei Central dopamine D2 receptors regulate plasma glucose levels in mice through autonomic nerves
description	Abstract Recent evidence suggests that the central nervous system (CNS) regulates plasma glucose levels, but the underlying mechanism is unclear. The present study investigated the role of dopaminergic function in the CNS in regulation of plasma glucose levels in mice. I.c.v. injection of neither the dopamine D1 receptor agonist SKF 38393 nor the antagonist SCH 23390 influenced plasma glucose levels. In contrast, i.c.v. injection of both the dopamine D2 receptor agonist quinpirole and the antagonist l-sulpiride increased plasma glucose levels. Hyperglycemia induced by quinpirole and l-sulpiride was absent in dopamine D2 receptor knockout mice. I.c.v. injection of quinpirole and l-sulpiride each increased mRNA levels of hepatic glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, which are the key enzymes for hepatic gluconeogenesis. Systemic injection of the β2 adrenoceptor antagonist ICI 118,551 inhibited hyperglycemia induced by l-sulpiride, but not by quinpirole. In contrast, hyperglycemia induced by quinpirole, but not by l-sulpiride, was inhibited by hepatic vagotomy. These results suggest that stimulation of central dopamine D2 receptors increases plasma glucose level by increasing hepatic glucose production through parasympathetic nerves, whereas inhibition of central dopamine D2 receptors increases plasma glucose level by increasing hepatic glucose production through sympathetic nerves.
format	article
author	Hiroko Ikeda Naomi Yonemochi Risa Mikami Manabu Abe Meiko Kawamura Rie Natsume Kenji Sakimura John L. Waddington Junzo Kamei
author_facet	Hiroko Ikeda Naomi Yonemochi Risa Mikami Manabu Abe Meiko Kawamura Rie Natsume Kenji Sakimura John L. Waddington Junzo Kamei
author_sort	Hiroko Ikeda
title	Central dopamine D2 receptors regulate plasma glucose levels in mice through autonomic nerves
title_short	Central dopamine D2 receptors regulate plasma glucose levels in mice through autonomic nerves
title_full	Central dopamine D2 receptors regulate plasma glucose levels in mice through autonomic nerves
title_fullStr	Central dopamine D2 receptors regulate plasma glucose levels in mice through autonomic nerves
title_full_unstemmed	Central dopamine D2 receptors regulate plasma glucose levels in mice through autonomic nerves
title_sort	central dopamine d2 receptors regulate plasma glucose levels in mice through autonomic nerves
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/47ef45d4b1a8495a87b36e3b35248b64
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Central dopamine D2 receptors regulate plasma glucose levels in mice through autonomic nerves

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