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The role of spinally located dopamine D2 receptors in the regulation of the blood glucose level in mice

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Abstract

Background

The possible role of dopamine D2 receptors located in the spinal cord in the regulation of the blood glucose level have not been investigated before.

Methods

In the present study, the effect of D2 receptor agonist and antagonist administered intrathecal (it) injection on the blood glucose level were examined in the Institute of Cancer Research (ICR) mice.

Results

We found that it injection with carmoxirole (D2 receptor agonist) caused an elevation of the blood glucose level in a dose-dependent manner. Carmoxirole-induced increase of the blood glucose was significantly attenuated by L-741,626 (D2 receptor antagonist). Previously, we indicated that intrathecal (it) treatment with 0.1 μg/5 μl pertussis toxin (PTX, a Gi/Go inhibitor) produces a hypoglycemic effect in ICR in a long-term manner. In the present study, it pretreatment with PTX for 6 days almost abolished the hyperglycemic effect induced by carmoxirole. The plasma insulin level was elevated by carmoxirole, and L-741,626 or PTX pretreatment reduced carmoxirole-induced increment of the insulin level. In addition, the plasma corticosterone level was increased by carmoxirole but it pretreatment with L-741,626 or PTX did not affect carmoxirole-induced increment of the corticosterone level.

Conclusion

Our results suggest that D2 receptors located in the spinal cord play an important role in the elevation of the blood glucose level. Spinally located inhibitory G-proteins appear to be involved in hyperglycemic effect induced by carmoxirole.

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Abbreviations

CNS:

Central nerves system

ICR:

Institute of Cancer Research

it :

Intrathecal

PEC:

Polyethylene glycol 400, ethanol, and sodium carboxymethylcellulose solution

PTX:

Pertussis toxin

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Funding

This research was supported by the Hallym Research Group Support Program of 2013 (HRF-G-2013-4).

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Author notes

  1. JaeSeung Hong and JingHui Feng contributed to the manuscript in equal measure.

Authors and Affiliations

  1. Department of Physical Education, Hallym University, 39 Hallymdaehak-gil, Chuncheon, Gangwon-do, 200-702, Republic of Korea

    JaeSeung Hong & JungSeok Park

  2. Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, 39 Hallymdaehak-gil, Chuncheon, Gangwon-do, 200-702, Republic of Korea

    JingHui Feng, HeeJung Lee, YunBeom Sim & HongWon Suh

  3. Department of Pharmacology, College of Medicine, Dankook University, Cheonan, Chungnam, 31116, Republic of Korea

    JinKoo Lee

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Contributions

All authors participated in the study design, interpretation, analysis, and review of the manuscript. Study concept and design, JSP and HWS; investigation, JSH and JKL; data curation, JKL and HJL; writing-original draft preparation, JSH and YBS; writing-review and editing, JHF; supervision and funding acquisition, HWS.

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Correspondence to HongWon Suh.

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Hong, J., Feng, J., Lee, J. et al. The role of spinally located dopamine D2 receptors in the regulation of the blood glucose level in mice. Pharmacol. Rep 72, 1666–1675 (2020). https://doi.org/10.1007/s43440-020-00126-x

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  • DOI: https://doi.org/10.1007/s43440-020-00126-x

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