Item – Theses Canada

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OCLC number
696906334
Link(s) to full text
LAC copy
LAC copy
Author
Bates, Holly Elizabeth,1978-
Title
Adaptation to intermittent restraint stress ameliorates hyperglycemia in ZDF rats by reducing hyperphagia, delaying [beta]-cell decompensation, and attenuating HPA hyperactivity.
Degree
Ph. D. -- University of Toronto, 2007
Publisher
Ottawa : Library and Archives Canada = Bibliothèque et Archives Canada, [2009]
Description
3 microfiches
Notes
Includes bibliographical references.
Abstract
Hyperactivity of the Hypothalamic-Pituitary-Adrenal (HPA) axis occurs in Type 2 Diabetes (T2DM), and is associated with reduced insulin sensitivity, glycemic control, and [beta]-cell function. Chronic stress is assumed to play a role in this HPA hyperactivity, despite the fact that human studies do not directly examine the effect of chronic stress on development of T2DM. We hypothesized that chronic intermittent restraint stress of male ZDF rats, a model of T2DM, would accelerate development of diabetes. Although acute restraint stress initially induced hyperglycemia, chronic intermittent stress surprisingly delayed development of fed and fasting hyperglycemia, without affecting glucose tolerance. Intermittent stress lowered food intake by 5-20% through a pathway that does not alter arcuate nucleus NPY and POMC mRNA expression. To distinguish between the effects of reduced food intake and of stress 'per se,' diet restricted/pair fed rats were studied. Intermittent stress delayed development of fed and fasting hyperglycemia in part through reduced food intake, but surprisingly also by food intake independent mechanisms. Primarily through the stress-induced reduction in food intake, intermittent stress maintained basal hyperinsulinemia and partially maintained [beta]-cell mass through [beta]-cell hyperplasia. Plasma lipidemia and adiposity did not appear to play a role in the delay of hyperglycemia. Interestingly, along with the delay of hyperglycemia, diet restriction and intermittent stress reduced central drive on the HPA axis. Intermittent stress further reduced basal hypercorticosteronemia compared to diet restriction, likely through improving hippocampal glucocorticoid feedback. Multiple regression analysis showed that basal corticosterone could predict ~20% of the variation in glycemia, which may explain the food intake independent delay of hyperglycemia by intermittent stress. In summary, in ZDF rats, intermittent restraint stress reduces hyperphagia, which maintains adequate [beta]-cell compensation and reduces central drive on the HPA axis. Independent of food intake, intermittent stress further delays hyperglycemia, presumably via adaptations in the HPA axis that prevent the hypercorticosteronemia caused by reduced food intake. These results suggest that instead of playing a causal role for the hyperactive HPA axis in T2DM, chronic stress may instead delay the deterioration in glucose homeostasis and ameriorate HPA hyperactivity.
ISBN
9780494396438
0494396431