| Summary: | Background: Estrogen deprivation in the postmenopausal women plays a critical role in progression of type 2 diabetes mellitus (T2DM). Aim: The present study investigated the overlaid effect of ovariectomy on T2DM and the possible underlying mechanism. Materials: Forty female Wistar rats were divided into four groups (10 rats each): sham control, ovariectomized control, sham diabetic and diabetic ovariectomized groups. At the end of experiment, estimation of body weight gain percentage, food intake, fasting blood glucose concentration, and insulin tolerance test were done. Then, rats were euthanized and blood samples were taken for measurement of serum concentration of insulin, HOMA-IR, lipid parameters, tumor necrosis factor-α, interleukin 1 beta, interleukin 4, interleukin 10, malondialdehyde and total thiol. Also, histopathological and immunohistochemical examination of the pancreas were done. Results: The present study revealed that ovariectomy aggravated the diabetic induced glucose metabolic disturbance as implied by impaired insulin tolerance test, increased insulin resistance alongside lipid dyshomeostasis. These metabolic disturbances might claim to exacerbation of oxidative stress and inflammatory response along with apparent histopathological and immunohistochemical changes on the pancreas. Conclusion: We concluded that metabolic disturbances induced by diabetes might be getting worse after ovariectomy via intensification of oxidative stress and inflammatory state. Keywords: Ovariectomy, T2DM, Pancreas, Oxidative stress, Inflammatory response, Menopause
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