Loss of Ovarian Estrogens Causes Only Mild Deterioration of Glucose Homeostasis in Female ZDF Rats Preventable by Voluntary Running Exercise

Studies on normoglycemic ovariectomized Sprague-Dawley rats have provided insights about the effects of estrogen deficiency on insulin resistance in lean individuals. It is not completely clear if subjects with pre-established obesity and insulin resistance are at greater risk of developing type 2 diabetes when ovarian estrogens are no longer secreted, and if physical activity can protect against this susceptibility. Contrasting with their male counterparts, obese and insulin resistant female ZDF (Zucker diabetic fatty) rats do not become hyperglycemic when fed a standard diet. The aim of the study was to evaluate the hypothesis that withdrawal of ovarian estrogens in insulin resistant female ZDF rats would trigger overt hyperglycemia, provided they remain physically inactive. Female ZDF rats underwent either an ovariectomy (OVX) or a simulated surgery (SHAM). Thereafter, OVX rats engaged either in voluntary wheel cage running (OVX-Active), or like the Sham rats, remained sedentary (OVX-Sed) for 6 weeks. Fasting glycemia, insulinemia, and glucose tolerance were not altered in OVX-Sed as compared to SHAM-Sed rats. However, OVX-Sed rats showed altered liver triglyceride and glycogen contents, increased pancreatic insulin content and reduced insulin-stimulated muscle pAKT as compared to SHAM-Sed rats. Physical activity in OVX rats lowered fasting glucose and insulin levels, improved glucose tolerance and insulin-stimulated skeletal muscle glucose uptake as compared to OVX-Sed rats. OVX-induced alterations in pancreatic insulin content and liver glycogen and triglyceride contents were significantly improved by physical activity. Loss of ovarian estrogens did not cause overt hyperglycemia in insulin-resistant female ZDF rats. Physical activity improved glucose homeostasis despite estrogen deficiency.