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Am J Physiol Endocrinol Metab 295: E947-E958, 2008. First published August 19, 2008; doi:10.1152/ajpendo.90378.2008
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Adaptation to intermittent stress promotes maintenance of β-cell compensation: comparison with food restriction

Holly E. Bates,1 Adam Sirek,1 Michael A. Kiraly,1 Jessica T. Y. Yue,1 Michael C. Riddell,4 Stephen G. Matthews,1,2,3 and Mladen Vranic1,3

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 {alpha}-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 {alpha}-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 {alpha}-cell mass that do not occur with food restriction.

restraint stress; Zucker diabetic fatty rat; islet dynamics; {alpha}-cell mass



Address for correspondence: H. E. Bates, Dept. of Physiology, Univ. of Toronto, 1 King's College Cir., Toronto, ON, Canada M5S 1A8 (e-mail: holdoug{at}yahoo.ca)


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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