REDUCTION IN HYPERGLYCEMIA BY MILD FOOD RESTRICTION IN STREPTOZOTOCIN-INDUCED DIABETIC RATS IMPROVES INSULIN SENSITIVITY

Hyperglycemia has been shown to contribute to the development and maintenance of insulin resistance in diabetic subjects and animal models of diabetes. Normalisation of circulating glucose levels is effective in restoring insulin action. The aim of the current study was to investigate the effects of mild food restriction on hyperglycemia in streptozotocin (STZ) treated (50 mg/kg) diabetic rats and to determine if the reductions in glycemia following food restriction were sufficient to alter insulin sensitivity. Food restriction was achieved in STZ diabetic and normal rats by limiting food access to two one-hourly meals daily and further in normal rats by restricting the feeding period to a single two-hour meal daily. Food intake was lowered by 39.7% (p < 0.01) in the food restricted STZ rats, without significant alteration in weight gain over 4 weeks. Similarly in the normal rats once and twice daily meals lowered food intake by 37.6% and 21.6% when compared to the ad-libitum fed group, respectively. After 3 weeks food restriction in the STZ diabetic rats mean plasma glucose levels over a 12 hour period were reduced by 13.9%, glucose levels after a 6 hr fast were reduced by 33% (p < 0.05). Plasma insulin levels remained unaltered by food restriction. After 4 weeks food restriction in STZ diabetic rats basal glucose turnover was reduced (p < 0.05) and the metabolic clearance rate of glucose (MCR) increased (p < 0.05). During the hyperinsulinemic clamp hepatic glucose output (HGO) was suppressed and MCR elevated more effectively in the food restricted STZ than the ad-libitum STZ rats. In normal rats food restriction resulted in increased basal and insulin-stimulated glucose disposal (MCR). We conclude that food restriction is effective in lowering plasma glucose levels and increases insulin sensitivity in STZ diabetic rats.