Abstract

BackgroundCalorie restriction (CR) has been well proved to be a powerful tool to improve metabolic health associated with aging; and many types of CR have been proposed. Intermittent CR has become a trend in recent years due to its better compliance than continuous CR every day. However, there are few studies that directly compare the interventional activity of intermittent CR vs continuous CR in metabolic disorders such as diabetes.MethodsIn this study, we analyzed two protocols of intermittent CR with the calorie-matched continuous CR in two diabetic mouse models including db/db and streptozotocin-treated mice. Intermittent CR was carried out by a fasting-mimicking diet (FMD, with 30% calorie intake of the control per day) for 2 days or 5 days (i.e., 2–5 or 5–9 regimes followed by free eating for 5 or 9 days respectively).ResultsIn the two diabetic mouse models, both intermittent CR and continuous CR significantly reduced fasting blood glucose level and improved insulin sensitivity. However, intermittent CR performed significantly better than continuous CR in improving glycemic control and insulin sensitivity in db/db mice. In addition, intermittent CR improved the glucose homeostasis of the db/db mice without causing loss of body weight. Analyses with the pancreatic islets reveal that intermittent CR profoundly elevated the number of insulin-positive cells in both diabetic mouse models.ConclusionsOur study indicated that both intermittent CR and continuous CR can lower fasting blood glucose level in the diabetic mice, while intermittent CR is better than the latter in improving glucose homeostasis in db/db mice.

Highlights

  • Weight loss, long considered as a key strategy to ameliorate the progression of type 2 diabetes and calorie restriction (CR), has been widely used to reduce obesity [1, 2]

  • Comparison of intermittent CR and continuous CR in db/ db mice We first compared the interventional effect of 2–5 regime of intermittent CR vs continuous CR in db/db mice that had severe type 2 diabetes due to extreme obesity caused by deficiency of leptin receptors

  • For implementation of intermittent CR, we used a fasting-mimicking diet (FMD) that is vegetable-based, and lower in protein and carbohydrates compared to normal chow [12]

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Summary

Introduction

Long considered as a key strategy to ameliorate the progression of type 2 diabetes and calorie restriction (CR), has been widely used to reduce obesity [1, 2]. It was found that calorie restriction is a significant factor in glycemic control in obese type 2 diabetic patients, in addition to the magnitude of weight loss [6]. We investigate whether CR-mediated weight loss is associated with glycemic control in diabetic mice. Calorie restriction (CR) has been well proved to be a powerful tool to improve metabolic health associated with aging; and many types of CR have been proposed. There are few studies that directly compare the interventional activity of intermittent CR vs continuous CR in metabolic disorders such as diabetes

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