Cargando…

Activation of Hindbrain Neurons Is Mediated by Portal-Mesenteric Vein Glucosensors During Slow-Onset Hypoglycemia

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 hypo...

Descripción completa

Detalles Bibliográficos
Autores principales: Bohland, MaryAnn, Matveyenko, Aleksey V., Saberi, Maziyar, Khan, Arshad M., Watts, Alan G., Donovan, Casey M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113064/
https://www.ncbi.nlm.nih.gov/pubmed/24727435
http://dx.doi.org/10.2337/db13-1600
_version_ 1782328242355568640
author Bohland, MaryAnn
Matveyenko, Aleksey V.
Saberi, Maziyar
Khan, Arshad M.
Watts, Alan G.
Donovan, Casey M.
author_facet Bohland, MaryAnn
Matveyenko, Aleksey V.
Saberi, Maziyar
Khan, Arshad M.
Watts, Alan G.
Donovan, Casey M.
author_sort Bohland, MaryAnn
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4113064
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher American Diabetes Association
record_format MEDLINE/PubMed
spelling pubmed-41130642015-08-01 Activation of Hindbrain Neurons Is Mediated by Portal-Mesenteric Vein Glucosensors During Slow-Onset Hypoglycemia Bohland, MaryAnn Matveyenko, Aleksey V. Saberi, Maziyar Khan, Arshad M. Watts, Alan G. Donovan, Casey M. Diabetes Complications 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. American Diabetes Association 2014-08 2014-07-17 /pmc/articles/PMC4113064/ /pubmed/24727435 http://dx.doi.org/10.2337/db13-1600 Text en © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
spellingShingle Complications
Bohland, MaryAnn
Matveyenko, Aleksey V.
Saberi, Maziyar
Khan, Arshad M.
Watts, Alan G.
Donovan, Casey M.
Activation of Hindbrain Neurons Is Mediated by Portal-Mesenteric Vein Glucosensors During Slow-Onset Hypoglycemia
title Activation of Hindbrain Neurons Is Mediated by Portal-Mesenteric Vein Glucosensors During Slow-Onset Hypoglycemia
title_full Activation of Hindbrain Neurons Is Mediated by Portal-Mesenteric Vein Glucosensors During Slow-Onset Hypoglycemia
title_fullStr Activation of Hindbrain Neurons Is Mediated by Portal-Mesenteric Vein Glucosensors During Slow-Onset Hypoglycemia
title_full_unstemmed Activation of Hindbrain Neurons Is Mediated by Portal-Mesenteric Vein Glucosensors During Slow-Onset Hypoglycemia
title_short Activation of Hindbrain Neurons Is Mediated by Portal-Mesenteric Vein Glucosensors During Slow-Onset Hypoglycemia
title_sort activation of hindbrain neurons is mediated by portal-mesenteric vein glucosensors during slow-onset hypoglycemia
topic Complications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113064/
https://www.ncbi.nlm.nih.gov/pubmed/24727435
http://dx.doi.org/10.2337/db13-1600
work_keys_str_mv AT bohlandmaryann activationofhindbrainneuronsismediatedbyportalmesentericveinglucosensorsduringslowonsethypoglycemia
AT matveyenkoalekseyv activationofhindbrainneuronsismediatedbyportalmesentericveinglucosensorsduringslowonsethypoglycemia
AT saberimaziyar activationofhindbrainneuronsismediatedbyportalmesentericveinglucosensorsduringslowonsethypoglycemia
AT khanarshadm activationofhindbrainneuronsismediatedbyportalmesentericveinglucosensorsduringslowonsethypoglycemia
AT wattsalang activationofhindbrainneuronsismediatedbyportalmesentericveinglucosensorsduringslowonsethypoglycemia
AT donovancaseym activationofhindbrainneuronsismediatedbyportalmesentericveinglucosensorsduringslowonsethypoglycemia