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

Abstract

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.

Dietary restriction preserves the mass and function of pancreatic β cells via cell kinetic regulation and suppression of oxidative/ER stress in diabetic mice

“…In the present study, we found that metabolic deterioration observed in db/db mice was ameliorated by caloric restriction, which was characterized as an increase in insulin secretory capacity. These results were consistent with those shown in previous reports using different animal model [26,27]. In this study, gene expressions of insulins 1 and 2 in diet-restricted db/db mice were not significantly higher than those in untreated db/db mice despite of a significant increase of insulin content in diet-treated mice.…”

No mantle formation in rodent islets—The prototype of islet revisited

“…A relative increase in alpha-cells present in the central core of the islet has been reported in many animal models of beta-cell deficiency (6–11) as well as in patients with type 2 diabetes (12, 13), and is often described as “disorganized islet architecture” based on “the prototype” structure. The disorganized architecture is thought to result from the collapse of the central beta-cell core due to beta-cell loss rather than alpha-cell hyperplasia.…”

Effects of glucocorticoids and exercise on pancreatic β‐cell function and diabetes development

“…GCs induce direct and indirect effects on various pathways in insulin synthesis and signalling in β‐cells . GCs target similar receptors and proteins in the β‐cells as they do in liver and skeletal muscle .…”