Title : The protective role of G-Protein coupled Estrogen Receptor (GPER) on postmenopausal diabetic cardiomyopathy
Diabetic cardiometabolic disorders are characterized by significant changes in cardiac metabolism and are increased in postmenopausal women, which emphasize the role of 17β-estradiol (E2). Despite this, there are few safe and effective pharmacological treatments for these disorders. The G protein-coupled estrogen receptor (GPER), which mediates the rapid effects of E2, has beneficial cardiac effects in both type 2 diabetes (T2D) and menopause. Based on genetic and pharmacological approaches, a growing body of experimental evidence highlights the role of GPER in E2 function and, in particular, the adjustment of metabolism and cardiovascular function, but its mechanism of action is not well understood. In general, our results showed that T2D leads to cardiovascular dysfunction, possibly due to a change in the amount of cardiac CD36, peroxisome proliferator-activated receptor α (PPARα), hexokinase 2 (HK2), glucose transport 4 (GLUT4), and inflammatory and anti-inflammatory cytokines. Furthermore, induction of the menopausal model can worsen the effects of diabetes. However, our results showed that the cardiovascular protective mechanism of the GPER in addition to correcting lipid and glycemic profiles, reducing insulin resistance, and increase in GPER level protein also reduces inflammatory cytokines and increases anti-inflammatory cytokines. Although all inflammatory cytokines are not affected by stimulation or inhibition of GPER, the ratio of inflammatory to anti-inflammatory cytokines decreases In relation to changes in cardiac metabolism, our results showed that the stimulation of GPER by increasing the expression of PPARα and HK2 leads to a decrease in cardiac content of glycogen, glucose, free fatty acids, and lipids. We conclude that G-1 as a GPER 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.
Keywords: Type 2 diabetes, 17β-estradiol, GPER, Menopause, Cardiovascular.
- How diabetes leads to changes in metabolism and heart function.
- How menopause can exacerbate the effects of diabetes on metabolism and heart function.
- How estrogen through its membrane receptor (GPER) can counteract the effects of menopause and diabetes on metabolism and heart function.