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The Rate of Fall of Blood Glucose Determines the Necessity of Forebrain-Projecting Catecholaminergic Neurons for Male Rat Sympathoadrenal Responses

Different onset rates of insulin-induced hypoglycemia use distinct glucosensors to activate sympathoadrenal counterregulatory responses (CRRs). Glucosensory elements in the portal-mesenteric veins are dispensable with faster rates when brain elements predominate, but are essential for responses to t...

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Autores principales: Jokiaho, Anne J., Donovan, Casey M., Watts, Alan G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113074/
https://www.ncbi.nlm.nih.gov/pubmed/24740574
http://dx.doi.org/10.2337/db13-1753
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author Jokiaho, Anne J.
Donovan, Casey M.
Watts, Alan G.
author_facet Jokiaho, Anne J.
Donovan, Casey M.
Watts, Alan G.
author_sort Jokiaho, Anne J.
collection PubMed
description Different onset rates of insulin-induced hypoglycemia use distinct glucosensors to activate sympathoadrenal counterregulatory responses (CRRs). Glucosensory elements in the portal-mesenteric veins are dispensable with faster rates when brain elements predominate, but are essential for responses to the slower-onset hypoglycemia that is common with insulin therapy. Whether a similar rate-associated divergence exists within more expansive brain networks is unknown. Hindbrain catecholamine neurons distribute glycemia-related information throughout the forebrain. We tested in male rats whether catecholaminergic neurons that project to the medial and ventromedial hypothalamus are required for sympathoadrenal CRRs to rapid- and slow-onset hypoglycemia and whether these neurons are differentially engaged as onset rates change. Using a catecholamine-specific neurotoxin and hyperinsulinemic-hypoglycemic clamps, we found that sympathoadrenal CRRs to slow- but not rapid-onset hypoglycemia require hypothalamus-projecting catecholaminergic neurons, the majority of which originate in the ventrolateral medulla. As determined with Fos, these neurons are differentially activated by the two onset rates. We conclude that 1) catecholaminergic projections to the hypothalamus provide essential information for activating sympathoadrenal CRRs to slow- but not rapid-onset hypoglycemia, 2) hypoglycemia onset rates have a major impact on the hypothalamic mechanisms that enable sympathoadrenal CRRs, and 3) hypoglycemia-related sensory information activates hindbrain catecholaminergic neurons in a rate-dependent manner.
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spelling pubmed-41130742015-08-01 The Rate of Fall of Blood Glucose Determines the Necessity of Forebrain-Projecting Catecholaminergic Neurons for Male Rat Sympathoadrenal Responses Jokiaho, Anne J. Donovan, Casey M. Watts, Alan G. Diabetes Complications Different onset rates of insulin-induced hypoglycemia use distinct glucosensors to activate sympathoadrenal counterregulatory responses (CRRs). Glucosensory elements in the portal-mesenteric veins are dispensable with faster rates when brain elements predominate, but are essential for responses to the slower-onset hypoglycemia that is common with insulin therapy. Whether a similar rate-associated divergence exists within more expansive brain networks is unknown. Hindbrain catecholamine neurons distribute glycemia-related information throughout the forebrain. We tested in male rats whether catecholaminergic neurons that project to the medial and ventromedial hypothalamus are required for sympathoadrenal CRRs to rapid- and slow-onset hypoglycemia and whether these neurons are differentially engaged as onset rates change. Using a catecholamine-specific neurotoxin and hyperinsulinemic-hypoglycemic clamps, we found that sympathoadrenal CRRs to slow- but not rapid-onset hypoglycemia require hypothalamus-projecting catecholaminergic neurons, the majority of which originate in the ventrolateral medulla. As determined with Fos, these neurons are differentially activated by the two onset rates. We conclude that 1) catecholaminergic projections to the hypothalamus provide essential information for activating sympathoadrenal CRRs to slow- but not rapid-onset hypoglycemia, 2) hypoglycemia onset rates have a major impact on the hypothalamic mechanisms that enable sympathoadrenal CRRs, and 3) hypoglycemia-related sensory information activates hindbrain catecholaminergic neurons in a rate-dependent manner. American Diabetes Association 2014-08 2014-07-17 /pmc/articles/PMC4113074/ /pubmed/24740574 http://dx.doi.org/10.2337/db13-1753 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
Jokiaho, Anne J.
Donovan, Casey M.
Watts, Alan G.
The Rate of Fall of Blood Glucose Determines the Necessity of Forebrain-Projecting Catecholaminergic Neurons for Male Rat Sympathoadrenal Responses
title The Rate of Fall of Blood Glucose Determines the Necessity of Forebrain-Projecting Catecholaminergic Neurons for Male Rat Sympathoadrenal Responses
title_full The Rate of Fall of Blood Glucose Determines the Necessity of Forebrain-Projecting Catecholaminergic Neurons for Male Rat Sympathoadrenal Responses
title_fullStr The Rate of Fall of Blood Glucose Determines the Necessity of Forebrain-Projecting Catecholaminergic Neurons for Male Rat Sympathoadrenal Responses
title_full_unstemmed The Rate of Fall of Blood Glucose Determines the Necessity of Forebrain-Projecting Catecholaminergic Neurons for Male Rat Sympathoadrenal Responses
title_short The Rate of Fall of Blood Glucose Determines the Necessity of Forebrain-Projecting Catecholaminergic Neurons for Male Rat Sympathoadrenal Responses
title_sort rate of fall of blood glucose determines the necessity of forebrain-projecting catecholaminergic neurons for male rat sympathoadrenal responses
topic Complications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113074/
https://www.ncbi.nlm.nih.gov/pubmed/24740574
http://dx.doi.org/10.2337/db13-1753
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