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Activation of G protein-coupled estrogen receptor inhibits endoplasmic reticulum stress in postmenopausal type 2 diabetic rats by upregulating SERCA2a
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Mohammad Amin Ghafari   , Zeinab Farhadi , Jalil Alizadehghalenoei , Hossein Azizian |
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Abstract: (201 Views) |
Introduction: Type 2 diabetes leads to the disruption of the protein folding process which causes accumulation of misfolded or unfolded proteins in the Endoplasmic reticulum (ER), a condition referred to as ER stress (ERS). Studies have shown that if menopause is accompanied by T2D, it enhances metabolic and cardiac disorders by influencing ER homeostasis, which emphasize the role of 17β-estradiol (E2). The G protein-coupled receptor 30 (GPR30), which mediates the rapid effects of E2, has beneficial cardiac effects in both type 2 diabetes (T2D) and menopause. Increasing evidence highlights the role of GPR30 in the adjustment of cardiac metabolism, but its mechanism of action is not well understood. In the current study, we used ovariectomized (OVA) diabetic rats’ models to evaluate the action of G-1 (GPR30 agonist) on ERS.
Methods and Materials: Animals were divided into three groups: OVA, OVA+T2D, and OVA+T2D+G-1. After induction of menopause and T2D, Diabetic postmenopausal rats were treated with G1 three days per week for six weeks.
Results: In general, our results showed that T2D leads to cardiac histopathological changes, increased GRP78 protein level as an ERS marker, and decreased SERCA2α protein level in cardiac OVA rats and stimulation of GPR30 counteracted these changes. In contrast these changes were reversed by G-1, so that G-1 improved cardiac histopathological changes, decreased GRP78 protein level, and increased SERCA2α protein level in cardiac OVA rats.
Conclusion: In relation to changes, we conclude that G-1 as a GPR30 agonist is a prototype candidate drug for potential translation into clinical applications. It is suggested that in future studies, firstly the role of other estrogen receptors in the cardiovascular protective action of this sex steroid in postmenopausal diabetic animals should be investigated, and secondly, the intracellular signaling pathway of the membrane receptor in diabetes should also be investigated.
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| Keywords: Type 2 diabetes, GPR30, Menopause, Endoplasmic reticulum stress |
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Full-Text [PDF 345 kb]
(27 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2024/02/21 | Accepted: 2023/08/10 | Published: 2023/08/10
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