Late introduction of low dose resveratrol and grape powder after estradiol depletion does not restore glucose tolerance in the ovariectomized rat.

Abstract

Background: Estrogen (E2) loss is associated with insulin resistance. Natural compounds such as resveratrol (RESV) have potential insulin sensitizing effects. Grape pomace powder (GP) also contains RESV and other antioxidants. However, the ability of realistic, attainable concentrations of RESV and GP to reverse glucose intolerance in E2 deficient rats has not yet been explored.

Purpose: The aim of the current study was to determine whether RESV and GP, in realistic amounts that could be achieved with supplementation, would be effective in restoring glucose tolerance in the ovariectomized (OVX) rat. Furthermore, there appears to be a critical time window following the loss of E2 when hormonal replacement is effective, with delayed treatment being ineffective and potentially detrimental. Therefore, we were particularly interested in examining the effectiveness of RESV and GP as a delayed treatment i.e. after the establishment of glucose intolerance, rather than administering at the onset of E2 loss. 

Results: In the present study, rats demonstrated impaired glucose tolerance, as determined by an intraperitoneal glucose tolerance test, 12 weeks after bilateral ovary removal. Subsequently, OVX animals were randomly placed into a sham or one of 3 treatment groups. The treatments were either i) a physiological oral dose of E2 (28µg/kg body mass), ii) RESV (5mg/kg body mass), or iii) GP (1.5g/100g of diet) for another 6 weeks. OVX animals were significantly heavier than non-OVX rats at the onset of glucose intolerance and this did not change throughout the treatment. None of the treatments restored glucose tolerance within the 6 weeks. Insulin tolerance did not worsen in OVX rats and was unaffected by treatment. Adipocyte size was generally increased in OVX animals and was not decreased with treatment.

Conclusions: In conclusion, delayed E2, RESV and GP treatment do not restore glucose tolerance in OVX rats. Low dose RESV and GP supplementation may not be effective alternatives to HRT to restore compromised glucose tolerance.         

Keywords: ovariectomy, estrogen, resveratrol, grape pomace, glucose tolerance, insulin tolerance, delayed treatment