Estrogen regulates duodenal glucose absorption by affecting estrogen receptor-α on glucose transporters

Weixi Shan; Jianhong Ding; Jingyu Xu; Qian Du; Changmei Chen; Qiushi Liao; Xiaoxu Yang; Jun Lou; Zhe Jin; Mingkai Chen; Rui Xie

doi:10.1016/j.mce.2023.112028

Estrogen regulates duodenal glucose absorption by affecting estrogen receptor-α on glucose transporters

Mol Cell Endocrinol. 2023 Sep 26:112028. doi: 10.1016/j.mce.2023.112028. Online ahead of print.

Authors

Weixi Shan¹, Jianhong Ding¹, Jingyu Xu¹, Qian Du¹, Changmei Chen¹, Qiushi Liao¹, Xiaoxu Yang¹, Jun Lou¹, Zhe Jin¹, Mingkai Chen², Rui Xie³

Affiliations

¹ Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, China; Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi, Guizhou, 563003, China.
² Department of Gastroenterology, Renmin Hospital of Wuhan University, 99 Zhang Zhidong Road, Wuhan, 430060, Hubei, China. Electronic address: chenmingkai@whu.edu.cn.
³ Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, China; Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi, Guizhou, 563003, China. Electronic address: xr19841029@aliyun.com.

PMID: 37769868
DOI: 10.1016/j.mce.2023.112028

Abstract

The mechanisms of estrogen in glucose metabolism are well established; however, its role in glucose absorption remains unclear. In this study, we investigated the effects of estrogen on glucose absorption in humans, mice, and SCBN intestinal epithelial cells. We first observed a correlation between estrogen and blood glucose in young women and found that glucose tolerance was significantly less in the premenstrual phase than in the preovulatory phase. Similarly, with decreased serum estradiol levels in ovariectomized mice, estrogen receptors alpha (ERα) and beta (ERβ) in the duodenum were reduced, and weight and abdominal fat increased significantly. The expression of sodium/glucose cotransporter 1 (SGLT1) and glucose transporter 2 (GLUT2) and glucose absorption in the duodenum decreased significantly. Estrogen significantly upregulated SGLT1 and GLUT2 expression in SCBN cells. Silencing of ERα, but not ERβ, reversed this trend, suggesting that ERα may be key to estrogen-regulating glucose transporters. A mechanistic study revealed that downstream, estrogen regulates the protein kinase C (PKC) pathway. Overall, our findings indicate that estrogen promotes glucose absorption, and estrogen and ERα deficiency can inhibit SGLT1 and GLUT2 expression through the PKC signaling pathway, thereby reducing glucose absorption.

Keywords: Duodenum; Estrogen; Estrogen receptor; Glucose absorption; Glucose transport proteins.