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Central dopamine D2 receptors regulate plasma glucose levels in mice through autonomic nerves
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 dopamin...
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Published in: | Scientific reports 2020-12, Vol.10 (1), p.22347-22347, Article 22347 |
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Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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 D
1
receptor agonist SKF 38393 nor the antagonist SCH 23390 influenced plasma glucose levels. In contrast, i.c.v. injection of both the dopamine D
2
receptor agonist quinpirole and the antagonist l-sulpiride increased plasma glucose levels. Hyperglycemia induced by quinpirole and l-sulpiride was absent in dopamine D
2
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 β
2
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 D
2
receptors increases plasma glucose level by increasing hepatic glucose production through parasympathetic nerves, whereas inhibition of central dopamine D
2
receptors increases plasma glucose level by increasing hepatic glucose production through sympathetic nerves. |
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ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/s41598-020-79292-0 |