Glucose absorption in the duodenum is modulated by an estrogen receptor α-dependent regulation of glucose transporter...

The mechanisms of estrogen in glucose metabolism are well established; however, the role of this hormone in glucose absorption remains unclear. In this study, we investigated the effects of estrogen on glucose absorption in humans, mice, and the human intestinal epithelium cell line SCBN.

The ovariectomized (OVX) animal model was established. Radioimmunoassay was used to detect the serum estradiol level. Blood insulin, glucose, and homeostatic model assessment of insulin resistance index were determined. Oral glucose tolerance test was used to detect the glucose tolerance of OVX mice and women aged 20-30 years. Ussing chamber experiments were performed to measure glucose absorption ex vivo in the duodenum of the mice. Western blot and immunohistochemistry were used to detect the expressions of estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), sodium/glucose cotransporter 1 (SGLT1), glucose transporter 2 (GLUT2), phosphorylated protein kinase C (PKC), p75 neurotrophin receptor and cluster of differentiation 36.

In women aged 20-30 years, we first observed a correlation between estrogen and blood glucose, with lower glucose tolerance in the premenstrual phase compared with the preovulatory phase. Similarly, compared with the controls, OVX mice showed increased body weight and abdominal fat, decreased levels of serum estradiol, and reduced duodenal (1) expression ERα and ERβ, (2) expression of SGLT1 and GLUT2, and (3) glucose absorption. In SCBN cells, estrogen upregulated SGLT1 and GLUT2 expression; silencing of ERα, but not ERβ, reversed this trend, suggesting that ERα is a key regulator. Mechanistically, estrogen modulates PKC signaling downstream.

Our findings suggest that, at least in premenopausal women and female mice, glucose absorption is in part regulated by estrogen via an ERα-dependent modulation of the functional expression of SGLT1 and GLUT2 in the duodenum.