Adaptation to intermittent stress promotes maintenance of -cell compensation: comparison with food restriction

Bates HE, Sirek A, Kiraly MA, Yue JT, Riddell MC, Matthews SG, Vranic M. Adaptation to intermittent stress promotes maintenance of -cell compensation: comparison with food restriction. Am J Physiol Endocrinol Metab 295: E947–E958, 2008. First published August 19, 2008; doi:10.1152/ajpendo.90378.2008.—Intermittent restraint stress delays hyperglycemia in ZDF rats better than pair feeding. We hypothesized that intermittent stress would preserve -cell mass through distinct mechanisms from food restriction. We studied temporal effects of intermittent stress on -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 -cell mass was not increased, and islets had fewer -cells that were hypertrophic. Both stress and food restriction partially preserved -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 -cell proliferation and reduced -cell hypertrophy, translating into 30% more -cells per islet after 13 wk. In contrast, food restriction did not improve insulin responses or -cell hyperplasia, exacerbated -cell hypertrophy, and resulted in fewer -cells and greater -cell mass than with stress. Thus, preservation of -cell mass with adaptation to intermittent stress is related to -cell hyperplasia, maintenance of insulin responses to glucose, and reductions in -cell mass that do not occur with food restriction.