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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. <jats:italic>In vitro<\/jats:italic>, neuronal activation or inhibition using either excitatory or inhibitory <jats:underline>d<\/jats:underline>esigner <jats:underline>r<\/jats:underline>eceptor <jats:underline>e<\/jats:underline>xclusively <jats:underline>a<\/jats:underline>ctivated by <jats:underline>d<\/jats:underline>esigner <jats:underline>d<\/jats:underline>rugs (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. <jats:italic>In vivo<\/jats:italic>, 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)\u00a0expression, 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.<\/jats:p>","DOI":"10.1038\/s41598-019-39490-x","type":"journal-article","created":{"date-parts":[[2019,2,25]],"date-time":"2019-02-25T11:03:08Z","timestamp":1551092588000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["A hindbrain inhibitory microcircuit mediates vagally-coordinated glucose regulation"],"prefix":"10.1038","volume":"9","author":[{"given":"Carie R.","family":"Boychuk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katalin Cs.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura E.","family":"Peterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7003-1553","authenticated-orcid":false,"given":"Jeffery A.","family":"Boychuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corwin R.","family":"Butler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel D.","family":"Derera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"McCarthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bret N.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,2,25]]},"reference":[{"key":"39490_CR1","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1038\/nm.4137","volume":"22","author":"RJ Seeley","year":"2016","unstructured":"Seeley, R. 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