Moderate calorie restriction to achieve normal weight reverses ß-cell dysfunction in diet-induced obese mice: involvement of autophagy.
Nutr Metab (Lond)
; 12: 34, 2015.
Article
em En
| MEDLINE
| ID: mdl-26445593
ABSTRACT
BACKGROUND:
Severe calorie restriction (CR) is shown to improve or even reverse ß-cell dysfunction in patients with obesity and type 2 diabetes mellitus. However, whether mild to moderate CR can reverse ß-cell dysfunction induced by obesity and the underlying mechanism remain unclear. Autophagy plays an important role in maintaining mass, architecture and function of ß-cells. While the impact of CR on ß-cell autophagy is unknown. This study aims to investigate the effects of moderate CR on ß-cell function and autophagy activity in diet-induced obese (DIO) mice.METHODS:
DIO C57BL/6 mice were subjected to 3 weeks of switching to normal chow (HF â NC group) or normal chow with 40 % CR (HF â NC CR group). Then hematoxylin-eosin and immunohistochemistry staining were performed to observe ß-cell morphology. ß-cell function was evaluated by intraperitoneal glucose tolerance test in vivo and static GSIS (glucose-stimulated insulin secretion) in isolated islets. ß-cell autophagy activity was determined by transmission electron microscope and western blot.RESULTS:
In the HF â NC CR group, CR normalized body weights, completely restored glucose tolerance, early-phase and second-phase insulin secretion, insulin sensitivity, and islet size. CR also normalized insulin content and glucose-stimulated insulin secretion in isolated islets in vitro. Furthermore, ß-cell autophagy level was increased in the HF â NC CR group, but AMPK phosphorylation remained unchanged. Although HF â NC mice achieved moderate weight loss and normal glucose tolerance, their insulin secretion was not improved compared with obese control mice, and additionally, ß-cell autophagy was not activated in these mice.CONCLUSIONS:
Moderate (40 %) CR to achieve normal weight reversed ß-cell dysfunction and insulin resistance, and restored glucose homeostasis in DIO mice. Furthermore, the up-regulation of ß-cell autophagy may play a role in this process, independent of AMPK activation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Nutr Metab (Lond)
Ano de publicação:
2015
Tipo de documento:
Article