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

Am J Physiol Endocrinol Metab. 2008 Oct;295(4):E947-58. doi: 10.1152/ajpendo.90378.2008. Epub 2008 Aug 19.


Intermittent restraint stress delays hyperglycemia in ZDF rats better than pair feeding. We hypothesized that intermittent stress would preserve beta-cell mass through distinct mechanisms from food restriction. We studied temporal effects of intermittent stress on beta-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 beta-cell mass was not increased, and islets had fewer beta-cells that were hypertrophic. Both stress and food restriction partially preserved beta-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 beta-cell proliferation and reduced beta-cell hypertrophy, translating into 30% more beta-cells per islet after 13 wk. In contrast, food restriction did not improve insulin responses or beta-cell hyperplasia, exacerbated beta-cell hypertrophy, and resulted in fewer beta-cells and greater alpha-cell mass than with stress. Thus, preservation of beta-cell mass with adaptation to intermittent stress is related to beta-cell hyperplasia, maintenance of insulin responses to glucose, and reductions in alpha-cell mass that do not occur with food restriction.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / physiology*
  • Animals
  • Blood Glucose / physiology
  • Bromodeoxyuridine
  • Caloric Restriction*
  • Cell Proliferation
  • Cell Size
  • Eating / physiology
  • Glucagon-Secreting Cells / physiology
  • Glucagon-Secreting Cells / ultrastructure
  • Glucose / pharmacology
  • Immunohistochemistry
  • Insulin / blood
  • Insulin-Secreting Cells / physiology*
  • Insulin-Secreting Cells / ultrastructure
  • Male
  • Pancreas / cytology
  • Pancreatic Ducts / cytology
  • Pancreatic Ducts / growth & development
  • Rats
  • Restraint, Physical
  • Stress, Psychological / physiopathology*


  • Blood Glucose
  • Insulin
  • Bromodeoxyuridine
  • Glucose