Neurochemical Mechanisms in the Hypothalamus and Attenuation of Compensatory Hormone Responses to Recurrent Hypoglycemia

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Neuroscience

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• De Vries, Martin Goos

Contributors dc:contributor

• J. Lee Beverly

• Health Sciences, Pathology

Language dc:language

eng

Identifier

(MiAaPQ)AAI3070287

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/82491