The Effects of Estrogen, Grape Pomace, and Resveratrol Supplementation on Glucose Tolerance and Insulin Signaling in Ovariectomized Rats.

Abstract

Estrogen (E2) loss results in increased visceral adiposity and impaired glucose tolerance. Estrogen replacement may restore insulin sensitivity if given shortly after menopause, but may be associated with side effects such as ovarian cancer. Other alternatives should be explored. Natural compounds such as resveratrol (RESV) and grape pomace (GP) have potential insulin sensitizing effects. To our knowledge, the efficacy of RESV and GP in restoring glucose tolerance in ovariectomized (OVX) rats has not been explored. Diet was administered ad libitum to sham control (SHAM) and OVX female rats until the onset of glucose intolerance in OVX rats as determined by an intraperitoneal glucose tolerance test (IPGTT). Subsequently, OVX animals were divided into treatment and control groups. The treatment groups received daily, one of i) a physiological oral dose of E2, ii) RESV, or iii) GP supplemented in the diet. Treatment continued for 6 wks followed by IPGTT and insulin tolerance tests. 2-3 d later, terminal surgeries were performed during which red and white gastrocnemius muscles, visceral adipose tissue (VAT) and liver were sampled to assess Akt response to insulin injection. VAT was stained to determine adipocyte size. None of the treatments restored normal glucose tolerance. Insulin tolerance was not worsened in OVX rats, and was unaffected with treatment. No difference in phosphorylation of the insulin signaling protein, Akt, was found after insulin injection in any tissue between SHAM and OVX rats. Adipocyte size was significantly increased in the OVX-E2 and OVX-RESV groups compared to SHAM. Delayed E2 replacement, RESV and GP were not effective in restoring normal glucose tolerance in OVX rats.