title: Activation of hindbrain neurons is mediated by portal-mesenteric vein glucosensors during slow-onset hypoglycemia.
abstract: Hypoglycemic detection at the portal-mesenteric vein (PMV) appears mediated by spinal afferents and is critical for the counter-regulatory response (CRR) to slow-onset, but not rapid-onset, hypoglycemia. Since rapid-onset hypoglycemia induces Fos protein expression in discrete brain regions, we hypothesized that denervation of the PMV or lesioning spinal afferents would suppress Fos expression in the dorsal medulla during slow-onset hypoglycemia, revealing a central nervous system reliance on PMV glucosensors. Rats undergoing PMV deafferentation via capsaicin, celiac-superior mesenteric ganglionectomy (CSMG), or total subdiaphragmatic vagotomy (TSV) were exposed to hyperinsulinemic-hypoglycemic clamps where glycemia was lowered slowly over 60-75 min. In response to hypoglycemia, control animals demonstrated a robust CRR along with marked Fos expression in the area postrema, nucleus of the solitary tract, and dorsal motor nucleus of the vagus. Fos expression was suppressed by 65-92% in capsaicin-treated animals, as was epinephrine (74%), norepinephrine (33%), and glucagon (47%). CSMG also suppressed Fos expression and CRR during slow-onset hypoglycemia, whereas TSV failed to impact either. In contrast, CSMG failed to impact upon Fos expression or the CRR during rapid-onset hypoglycemia. Peripheral glucosensory input from the PMV is therefore required for activation of hindbrain neurons and the full CRR during slow-onset hypoglycemia.
authors.affiliation: Department of Biological Sciences and Center for NeuroMetabolic Interactions, University of Southern California, Los Angeles, CA.
authors.forename: MaryAnn
authors.initials: M
authors.lastname: Bohland
authors.affiliation: Department of Biological Sciences and Center for NeuroMetabolic Interactions, University of Southern California, Los Angeles, CA.
authors.forename: Aleksey V
authors.initials: AV
authors.lastname: Matveyenko
authors.affiliation: Department of Biological Sciences and Center for NeuroMetabolic Interactions, University of Southern California, Los Angeles, CA.
authors.forename: Maziyar
authors.initials: M
authors.lastname: Saberi
authors.affiliation: Department of Biological Sciences and Center for NeuroMetabolic Interactions, University of Southern California, Los Angeles, CA.
authors.forename: Arshad M
authors.initials: AM
authors.lastname: Khan
authors.affiliation: Department of Biological Sciences and Center for NeuroMetabolic Interactions, University of Southern California, Los Angeles, CA.
authors.forename: Alan G
authors.initials: AG
authors.lastname: Watts
authors.affiliation: Department of Biological Sciences and Center for NeuroMetabolic Interactions, University of Southern California, Los Angeles, CA donovan@usc.edu.
authors.forename: Casey M
authors.initials: CM
authors.lastname: Donovan
mesh_terms: D000818:Animals; D002211:Capsaicin; D015171:Ganglionectomy; D005786:Gene Expression Regulation / Q000502:physiology; D015309:Glucose Clamp Technique; D007003:Hypoglycemia / Q000378:metabolism*; D008297:Male; D008642:Mesenteric Veins / Q000502:physiology*; D016761:Oncogene Proteins v-fos / Q000235:genetics / Q000378:metabolism; D011169:Portal Vein / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000502:physiology*; D012249:Rhombencephalon / Q000166:cytology*; D014628:Vagotomy
chemical_list: D016761:Oncogene Proteins v-fos; D011956:Receptors, Cell Surface; C027786:glucose receptor; D002211:Capsaicin
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