Adaptation to intermittent stress promotes maintenance of beta-cell compensation: comparison with food restriction.
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.
Bates
Holly E
HE
Department of Physiology, University of Toronto, Toronto, Ontario, Canada. holdoug@yahoo.ca
Sirek
Adam
A
Kiraly
Michael A
MA
Yue
Jessica T Y
JT
Riddell
Michael C
MC
Matthews
Stephen G
SG
Vranic
Mladen
M
D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000502:physiology; D001973:Bromodeoxyuridine; D031204:Caloric Restriction; D049109:Cell Proliferation; D048429:Cell Size; D004435:Eating / Q000502:physiology; D050416:Glucagon-Secreting Cells / Q000502:physiology / Q000648:ultrastructure; D005947:Glucose / Q000494:pharmacology; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D010179:Pancreas / Q000166:cytology; D010183:Pancreatic Ducts / Q000166:cytology / Q000254:growth & development; D051381:Rats; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000503:physiopathology*
D001786:Blood Glucose; D007328:Insulin; D001973:Bromodeoxyuridine; D005947:Glucose