A hindbrain inhibitory microcircuit mediates vagally-coordinated glucose regulation

Carie Boychuk, Katalin Cs Smith, Laura E. Peterson, Jeffery A. Boychuk, Corwin R. Butler, Isabel D. Derera, John J. McCarthy, Bret N. Smith

Research output: Contribution to journalArticle

Abstract

Neurons in the brainstem dorsal vagal complex integrate neural and humoral signals to coordinate autonomic output to viscera that regulate a variety of physiological functions, but how this circuitry regulates metabolism is murky. We tested the hypothesis that premotor, GABAergic neurons in the nucleus tractus solitarius (NTS) form a hindbrain micro-circuit with preganglionic parasympathetic motorneurons of the dorsal motor nucleus of the vagus (DMV) that is capable of modulating systemic blood glucose concentration. In vitro, neuronal activation or inhibition using either excitatory or inhibitory designer receptor exclusively activated by designer drugs (DREADDs) constructs expressed in GABAergic NTS neurons increased or decreased, respectively, action potential firing of GABAergic NTS neurons and downstream synaptic inhibition of the DMV. In vivo, DREADD-mediated activation of GABAergic NTS neurons increased systemic blood glucose concentration, whereas DREADD-mediated silencing of these neurons was without effect. The DREADD-induced hyperglycemia was abolished by blocking peripheral muscarinic receptors, consistent with the hypothesis that altered parasympathetic drive mediated the response. This effect was paralleled by elevated serum glucagon and hepatic phosphoenolpyruvate carboxykinase 1 (PEPCK1) expression, without affecting insulin levels or muscle metabolism. Activity in a hindbrain inhibitory microcircuit is sufficient to modulate systemic glucose concentration, independent of insulin secretion or utilization.

Original languageEnglish (US)
Article number2722
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019
Externally publishedYes

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Rhombencephalon
Designer Drugs
Solitary Nucleus
Neurons
Glucose
Blood Glucose
Insulin
GABAergic Neurons
Phosphoenolpyruvate
Viscera
Muscarinic Receptors
Glucagon
Hyperglycemia
Action Potentials
Brain Stem
Muscles
Liver
Serum

ASJC Scopus subject areas

  • General

Cite this

Boychuk, C., Smith, K. C., Peterson, L. E., Boychuk, J. A., Butler, C. R., Derera, I. D., ... Smith, B. N. (2019). A hindbrain inhibitory microcircuit mediates vagally-coordinated glucose regulation. Scientific Reports, 9(1), [2722]. https://doi.org/10.1038/s41598-019-39490-x

A hindbrain inhibitory microcircuit mediates vagally-coordinated glucose regulation. / Boychuk, Carie; Smith, Katalin Cs; Peterson, Laura E.; Boychuk, Jeffery A.; Butler, Corwin R.; Derera, Isabel D.; McCarthy, John J.; Smith, Bret N.

In: Scientific Reports, Vol. 9, No. 1, 2722, 01.12.2019.

Research output: Contribution to journalArticle

Boychuk, C, Smith, KC, Peterson, LE, Boychuk, JA, Butler, CR, Derera, ID, McCarthy, JJ & Smith, BN 2019, 'A hindbrain inhibitory microcircuit mediates vagally-coordinated glucose regulation', Scientific Reports, vol. 9, no. 1, 2722. https://doi.org/10.1038/s41598-019-39490-x
Boychuk, Carie ; Smith, Katalin Cs ; Peterson, Laura E. ; Boychuk, Jeffery A. ; Butler, Corwin R. ; Derera, Isabel D. ; McCarthy, John J. ; Smith, Bret N. / A hindbrain inhibitory microcircuit mediates vagally-coordinated glucose regulation. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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