Document Detail


A role for the forebrain in mediating time-of-day differences in glucocorticoid counterregulatory responses to hypoglycemia in rats.
MedLine Citation:
PMID:  17823259     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The time of day influences the magnitude of ACTH and corticosterone responses to hypoglycemia. However, little is known about the mechanisms that impart these time-of-day differences on neuroendocrine CRH neurons in the hypothalamic paraventricular nucleus (PVH). Rats received 0-3 U/kg insulin (or 0.9% saline) to achieve a range of glucose nadir concentrations. Brains were processed to identify phosphorylated ERK1/2 (phospho-ERK1/2)-immunoreactive cells in the PVH and hindbrain and CRH heteronuclear RNA in the PVH. Hypoglycemia did not stimulate ACTH and corticosterone responses in animals unless a glucose concentration of approximately 3.15 mM or below was reached. Critically the glycemic thresholds required to stimulate ACTH and corticosterone release in the morning and night were indistinguishable. Yet glucose concentrations below the estimated glycemic threshold correlated with a greater increase in corticosterone, ACTH, and phospho-ERK1/2-immunoreactive neurons in the PVH at night, compared with morning. In these same animals, the number of phospho-ERK1/2-immunoreactive neurons in the medial part of the nucleus of the solitary tract was unchanged at both times of day. These data collectively support a model whereby changes in forebrain mechanisms alter the sensitivity of neuroendocrine CRH to the hypoglycemia-related information conveyed by ascending catecholaminergic afferents. Circadian clock-driven processes together with glucose-sensing elements in the forebrain would seem to be strong contenders for mediating these effects.
Authors:
Lori M Gorton; Arshad M Khan; Maryann Bohland; Graciela Sanchez-Watts; Casey M Donovan; Alan G Watts
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural     Date:  2007-09-06
Journal Detail:
Title:  Endocrinology     Volume:  148     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-11-16     Completed Date:  2008-06-17     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6026-39     Citation Subset:  AIM; IM    
Affiliation:
The Neuroscience Research Institute, Hedco Neuroscience Building, University of Southern California, Los Angeles, CA 90089-2520, USA.
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MeSH Terms
Descriptor/Qualifier:
Adrenocorticotropic Hormone / blood
Animals
Blood Glucose / metabolism
Circadian Rhythm / physiology
Corticosterone / blood
Glucagon / blood
Glucocorticoids / blood
Hypoglycemia / blood,  physiopathology*
Hypoglycemic Agents / administration & dosage*
Immunohistochemistry
Insulin / administration & dosage*,  blood
Male
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Prosencephalon / drug effects*,  physiopathology
Rats
Rats, Sprague-Dawley
Time Factors
Grant Support
ID/Acronym/Agency:
DK 062471/DK/NIDDK NIH HHS; DK 55257/DK/NIDDK NIH HHS; MH 071108/MH/NIMH NIH HHS; NS 029728/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Glucocorticoids; 0/Hypoglycemic Agents; 11061-68-0/Insulin; 50-22-6/Corticosterone; 9002-60-2/Adrenocorticotropic Hormone; 9007-92-5/Glucagon; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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