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Departments of 1Physiology, 2Obstetrics and Gynecology, and 3Medicine, University of Toronto; and 4School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada
Submitted 18 April 2008 ; accepted in final form 13 August 2008
Intermittent restraint stress delays hyperglycemia in ZDF rats better than pair feeding. We hypothesized that intermittent stress would preserve β-cell mass through distinct mechanisms from food restriction. We studied temporal effects of intermittent stress on β-cell compensation during pre-, early, and late diabetes. Six-week-old obese male ZDF rats were restraint-stressed 1 h/day, 5 days/wk for 0, 3, 6, or 13 wk and compared with age-matched obese ZDF rats that had been food restricted for 13 wk, and 19-wk-old lean ZDF rats. Thirteen weeks of stress and food restriction lowered cumulative food intake 10–15%. Obese islets were fibrotic and disorganized and not improved by stress or food restriction. Obese pancreata had islet hyperplasia and showed evidence of neogenesis, but by 19 wk old β-cell mass was not increased, and islets had fewer β-cells that were hypertrophic. Both stress and food restriction partially preserved β-cell mass at 19 wk old via islet hypertrophy, whereas stress additionally lowered
-cell mass. Concomitant with maintenance of insulin responses to glucose, stress delayed the sixfold decline in β-cell proliferation and reduced β-cell hypertrophy, translating into 30% more β-cells per islet after 13 wk. In contrast, food restriction did not improve insulin responses or β-cell hyperplasia, exacerbated β-cell hypertrophy, and resulted in fewer β-cells and greater
-cell mass than with stress. Thus, preservation of β-cell mass with adaptation to intermittent stress is related to β-cell hyperplasia, maintenance of insulin responses to glucose, and reductions in
-cell mass that do not occur with food restriction.
restraint stress; Zucker diabetic fatty rat; islet dynamics;
-cell mass
Address for reprint requests: M. Vranic, Rm. 3363, Medical Sciences Bldg., Dept. of Physiology, Univ. of Toronto, 1 King's College Cir., Toronto, ON, Canada M5S 1A8 (e-mail: mladen.vranic{at}utoronto.ca)
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