Abstract: Abstract: Objective To investigate whether modest calorie restriction (CR) could reverse islet β-cell morphology and function disorder induced by obesity. Methods Male C57BL/6 mice were fed high fat diet (HF) for 8 weeks to create an diet-induced obese (DIO) model. Then they were divided into four groups: NC AL (normal chow, ad libitum), HF AL, HF→ NC (HF switching to NC) and HF→NC CR (40% CR). There were 20 mice in each group. These treatments continued for 3 weeks. At the end of the experiment, pancreas tissues were removed for insulin immunohistochemistry staining, to quantify β-cell area. Meanwhile, introperitoneal glucose tolerance test and insulin tolerance test were performed to evaluate early- phase insulin secretion, second-phase insulin secretion and insulin sensitivity. In addition, islets were isolated, the static glucose-stimulated insulin secretion and insulin content were measured in isolated islets. Results At the end of the experiment, HF AL mice showed significant obesity, increased β - cell area, impaired glucose intolerance, decreased tendency in early-phase insulin secretion and insulin resistance. At the same time, the in vitro isolated islet experiment displayed the increased insulin content and defective insulin secretion. The basal insulin secretion increased by 30.6%, while insulin secretion decreased by 52.1% under the condition of 16.7 mmol/L glucose stimulation. In the HF→NC group, after 3 weeks of intervention, the glucose tolerance returned to normal, body weights decreased. The early phase insulin secretion and insulin secretion stimulated by the high glucose in isolated islets of mice were not improved in HF NC group compared with those in HF AL group. After 3 weeks of dietary restriction intervention, body weights, beta cell area, glucose tolerance, early phase insulin secretion, insulin sensitivity, the basal insulin secretion and high glucose-stimulated insulin secretion in vitro returned to normal in HF→NC CR group. Conclusion The moderate (40%) calorie restriction to normal body weight can reverse the defective insulin secretion and normalize glucose tolerance in DIO mice.

Key words: obesity, body weight, calorie restriction, islet β-cell