Neurochemical Mechanisms in the Hypothalamus and Attenuation of Compensatory Hormone Responses to Recurrent Hypoglycemia
De Vries, Martin Goos
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https://hdl.handle.net/2142/82491
Description
Title
Neurochemical Mechanisms in the Hypothalamus and Attenuation of Compensatory Hormone Responses to Recurrent Hypoglycemia
Author(s)
De Vries, Martin Goos
Issue Date
2002
Doctoral Committee Chair(s)
J. Lee Beverly
Department of Study
Neuroscience
Discipline
Neuroscience
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Health Sciences, Pathology
Language
eng
Abstract
For the purpose of testing this hypothesis a new rat model of recurrent hypoglycemia was used in combination with in vivo microdialysis. This enabled the simultaneous evaluation of circulating glucose and hormones, as well as extracellular concentrations of glucose and norepinephrine (NE) in discrete hypothalamic nuclei. It was demonstrated that attenuated autonomic activation to recurrent hypoglycemia in rats is not caused by a previously presumed maladaptive increase of glucose uptake by the brain. The fall in brain glucose concentration is proportional to that in the blood, and this fall is not prevented during recurrent hypoglycemia. Moreover, noradrenergic neurotransmitter systems in the hypothalamus are activated to a decrease in ambient glucose, and their responsiveness is preserved after recurrent daily hypoglycemic episodes on three consecutive days. From the present work it became evident that the observed increase in liver glycogen content after recurrent hypoglycemia plays an essential role in the development of hypoglycemia unawareness. In contrast to fed controls, compensatory hormone responses during recurrent hypoglycemia were not attenuated when liver glycogen was depleted after an overnight fast. It is suggested that increased hepatic glycogen facilitates restoration of euglycemia, and thus alleviates extrahepatic compensatory processes.
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