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

被引:14
作者
Bates, Holly E. [1 ]
Sirek, Adam [1 ]
Kiraly, Michael A. [1 ]
Yue, Jessica T. Y. [1 ]
Riddell, Michael C. [4 ]
Matthews, Stephen G. [1 ,2 ,3 ]
Vranic, Mladen [1 ,3 ]
机构
[1] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada
[2] Univ Toronto, Dept Obstet & Gynecol, Toronto, ON M5S 1A8, Canada
[3] Univ Toronto, Dept Med, Toronto, ON M5S 1A8, Canada
[4] York Univ, Sch Kinesiol & Hlth Sci, Toronto, ON M3J 2R7, Canada
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 2008年 / 295卷 / 04期
基金
加拿大自然科学与工程研究理事会; 加拿大健康研究院;
关键词
restraint stress; Zucker diabetic fatty rat; islet dynamics; alpha-cell mass;
D O I
10.1152/ajpendo.90378.2008
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 beta-cell mass that do not occur with food restriction.
引用
收藏
页码:E947 / E958
页数:12
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