Estrogen regulates duodenal glucose absorption through the effect of estrogen receptor-α on glucose transporters

Abstract Estrogen deficiency is an important reason for the obesity of menopause, but the specific mechanism is unclear. Here, we investigated the effect of estrogen on glucose absorption. The experiments were performed in human, mice and SCBN cells. We first observed the correlation between estrogen and blood glucose in women, which found that blood glucose was significantly higher in the premenstrual phase than in the preovulatory phase of young women. Similarly, with serum estradiol level decreased in ovariectomized (OVX) mice, ER-α and ER-β in the duodenum reduced, the weight, abdominal fat and blood glucose increased significantly. However, interestingly, the expression of SGLT1 and GLUT2 and the glucose absorption in duodenal decreased significantly. It was further confirmed that estrogen could significantly up-regulate the expression of SGLT1 and GLUT2 in SCBN cells, and this trend can be reversed after silencing ER-α, but it doesn’t work after silencing ER-β, suggesting ER-α may be the key receptor of estrogen regulating glucose transporter. Mechanism study found that estrogen downstream can activate PKC pathway. Overall, our findings indicate that estrogen promotes glucose absorption, estrogen and its receptor (ER-α) deficiency can inhibit the expression of SGLT1 and GLUT2 through PKC signaling pathway, thereby reducing the glucose absorption.