واسطه گری سیرتوئینهای ۱/۳ در اثرات محافظتی قلبی گیرنده غشائی استروژن در موشهای بزرگ آزمایشگاهی دیابتی نوع ۲ فاقد تخمدان. (Persian)

Introduction: Metabolic disorders caused by type 2 diabetes (T2D), such as changes in mitochondrial function and heart metabolism, are major causes of cardiovascular disorders (CVD) in post-menopausal women. One of the mechanisms of disruption of the physiological function of mitochondria is post-translational change in proteins by sirtuins. Estrogen, and in particular its membrane receptor, have cardioprotective effects in diabetic-menopausal animal models by improving metabolic status. We hypothesized that in post-menopausal diabetic animals, G-1 as a selective G protein-coupled receptor 30 (GPR30) agonist may be able to regulate mitochondrial function by regulating sirtuins, thereby improving cardiac function. Methods and Materials: In the current study, we used ovariectomized (OVA) diabetic rat model to evaluate the action of G-1 (GPR30 agonist) on sirtuins and their signaling pathway. Animals were divided into five groups: ShamControl, T2D, OVA+T2D, OVA+T2D+Vehicle, and OVA+T2D+G-1. T2D induced by an HFD and low dose of streptozotocin and G-1 administrated for six weeks after the confirmation of T2D . Results: Our results depict that, T2D decreased cardiac levels of Sirt1, Sirt2, Sirt3, Sirt6, and p-AMPK. Also, the induction of the menopausal model exacerbated these changes. In contrast these changes were reversed by activation of GPR30, so that G-1 as a GPR30 agonist increased cardiac levels of Sirt1, Sirt3, and p-AMPK . Conclusions: In this research we present evidence of the cardioprotective effects of GPR30 operating through Sirt1, Sirt3, and p-AMPK. Our results suggest that increasing SIRTs and p-AMPK levels offer new therapeutic approaches for the treatment of the diabetic cardiomyopathy. [ABSTRACT FROM AUTHOR]

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