title: Functional identification of a neurocircuit regulating blood glucose.
abstract: Previous studies implicate the hypothalamic ventromedial nucleus (VMN) in glycemic control. Here, we report that selective inhibition of the subset of VMN neurons that express the transcription factor steroidogenic-factor 1 (VMN(SF1) neurons) blocks recovery from insulin-induced hypoglycemia whereas, conversely, activation of VMN(SF1) neurons causes diabetes-range hyperglycemia. Moreover, this hyperglycemic response is reproduced by selective activation of VMN(SF1) fibers projecting to the anterior bed nucleus of the stria terminalis (aBNST), but not to other brain areas innervated by VMN(SF1) neurons. We also report that neurons in the lateral parabrachial nucleus (LPBN), a brain area that is also implicated in the response to hypoglycemia, make synaptic connections with the specific subset of glucoregulatory VMN(SF1) neurons that project to the aBNST. These results collectively establish a physiological role in glucose homeostasis for VMN(SF1) neurons and suggest that these neurons are part of an ascending glucoregulatory LPBN→VMN(SF1)→aBNST neurocircuit.
authors.affiliation: Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington, Seattle, WA 98195;
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Meek
authors.affiliation: Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington, Seattle, WA 98195;
authors.forename: Jarrell T
authors.initials: JT
authors.lastname: Nelson
authors.affiliation: Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington, Seattle, WA 98195;
authors.forename: Miles E
authors.initials: ME
authors.lastname: Matsen
authors.affiliation: Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington, Seattle, WA 98195;
authors.forename: Mauricio D
authors.initials: MD
authors.lastname: Dorfman
authors.affiliation: Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington, Seattle, WA 98195;
authors.forename: Stephan J
authors.initials: SJ
authors.lastname: Guyenet
authors.affiliation: Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington, Seattle, WA 98195;
authors.forename: Vincent
authors.initials: V
authors.lastname: Damian
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI 48105;
authors.forename: Margaret B
authors.initials: MB
authors.lastname: Allison
authors.affiliation: Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington, Seattle, WA 98195;
authors.forename: Jarrad M
authors.initials: JM
authors.lastname: Scarlett
authors.affiliation: Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington, Seattle, WA 98195;
authors.forename: Hong T
authors.initials: HT
authors.lastname: Nguyen
authors.affiliation: Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington, Seattle, WA 98195;
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Thaler
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI 48105;
authors.forename: David P
authors.initials: DP
authors.lastname: Olson
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48105.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Myers
authors.affiliation: Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington, Seattle, WA 98195;
authors.forename: Michael W
authors.initials: MW
authors.lastname: Schwartz
authors.affiliation: Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington, Seattle, WA 98195; gjmorton@u.washington.edu.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Morton
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D007328:Insulin / Q000008:administration & dosage; D051379:Mice; D009475:Neurons, Afferent / Q000502:physiology*; D014697:Ventromedial Hypothalamic Nucleus / Q000166:cytology / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D007328:Insulin
keywords: bed nucleus of the stria terminalis; counter regulation; glucoregulatory circuit; hyperglycemia; ventromedial nucleus