Glucose absorption in the duodenum is modulated by an estrogen receptor α-dependent regulation of glucose transporter functional expression
Introduction 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 SCB...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2025-07-01
|
| Series: | BMJ Open Diabetes Research & Care |
| Online Access: | https://drc.bmj.com/content/13/4/e004914.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849730417317380096 |
|---|---|
| author | Xiaoxu Yang Qian Du Rui Xie Jianhong Ding Weixi Shan Jingyu Xu Changmei Chen Qiushi Liao Jun Lou Zhe Jin Mingkai Chen |
| author_facet | Xiaoxu Yang Qian Du Rui Xie Jianhong Ding Weixi Shan Jingyu Xu Changmei Chen Qiushi Liao Jun Lou Zhe Jin Mingkai Chen |
| author_sort | Xiaoxu Yang |
| collection | DOAJ |
| description | Introduction 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.Research design and methods 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.Results 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.Conclusions 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. |
| format | Article |
| id | doaj-art-0d6373b1bcc6439f8ac97f42e6fea7e8 |
| institution | DOAJ |
| issn | 2052-4897 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open Diabetes Research & Care |
| spelling | doaj-art-0d6373b1bcc6439f8ac97f42e6fea7e82025-08-20T03:08:52ZengBMJ Publishing GroupBMJ Open Diabetes Research & Care2052-48972025-07-0113410.1136/bmjdrc-2025-004914Glucose absorption in the duodenum is modulated by an estrogen receptor α-dependent regulation of glucose transporter functional expressionXiaoxu Yang0Qian Du1Rui Xie2Jianhong Ding3Weixi Shan4Jingyu Xu5Changmei Chen6Qiushi Liao7Jun Lou8Zhe Jin9Mingkai Chen10Zunyi Medical University, Zunyi, Guizhou, ChinaDepartment of Endoscopy and Digestive System, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, ChinaDepartment of Endoscopy and Digestive System, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, ChinaDepartment of Endoscopy and Digestive System, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, ChinaZunyi Medical University, Zunyi, Guizhou, ChinaGuizhou Medical University, Guiyang, Guizhou, ChinaZunyi Medical University, Zunyi, Guizhou, ChinaZunyi Medical University, Zunyi, Guizhou, ChinaZunyi Medical University, Zunyi, Guizhou, ChinaZunyi Medical University, Zunyi, Guizhou, ChinaDepartment of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaIntroduction 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.Research design and methods 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.Results 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.Conclusions 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.https://drc.bmj.com/content/13/4/e004914.full |
| spellingShingle | Xiaoxu Yang Qian Du Rui Xie Jianhong Ding Weixi Shan Jingyu Xu Changmei Chen Qiushi Liao Jun Lou Zhe Jin Mingkai Chen Glucose absorption in the duodenum is modulated by an estrogen receptor α-dependent regulation of glucose transporter functional expression BMJ Open Diabetes Research & Care |
| title | Glucose absorption in the duodenum is modulated by an estrogen receptor α-dependent regulation of glucose transporter functional expression |
| title_full | Glucose absorption in the duodenum is modulated by an estrogen receptor α-dependent regulation of glucose transporter functional expression |
| title_fullStr | Glucose absorption in the duodenum is modulated by an estrogen receptor α-dependent regulation of glucose transporter functional expression |
| title_full_unstemmed | Glucose absorption in the duodenum is modulated by an estrogen receptor α-dependent regulation of glucose transporter functional expression |
| title_short | Glucose absorption in the duodenum is modulated by an estrogen receptor α-dependent regulation of glucose transporter functional expression |
| title_sort | glucose absorption in the duodenum is modulated by an estrogen receptor α dependent regulation of glucose transporter functional expression |
| url | https://drc.bmj.com/content/13/4/e004914.full |
| work_keys_str_mv | AT xiaoxuyang glucoseabsorptionintheduodenumismodulatedbyanestrogenreceptoradependentregulationofglucosetransporterfunctionalexpression AT qiandu glucoseabsorptionintheduodenumismodulatedbyanestrogenreceptoradependentregulationofglucosetransporterfunctionalexpression AT ruixie glucoseabsorptionintheduodenumismodulatedbyanestrogenreceptoradependentregulationofglucosetransporterfunctionalexpression AT jianhongding glucoseabsorptionintheduodenumismodulatedbyanestrogenreceptoradependentregulationofglucosetransporterfunctionalexpression AT weixishan glucoseabsorptionintheduodenumismodulatedbyanestrogenreceptoradependentregulationofglucosetransporterfunctionalexpression AT jingyuxu glucoseabsorptionintheduodenumismodulatedbyanestrogenreceptoradependentregulationofglucosetransporterfunctionalexpression AT changmeichen glucoseabsorptionintheduodenumismodulatedbyanestrogenreceptoradependentregulationofglucosetransporterfunctionalexpression AT qiushiliao glucoseabsorptionintheduodenumismodulatedbyanestrogenreceptoradependentregulationofglucosetransporterfunctionalexpression AT junlou glucoseabsorptionintheduodenumismodulatedbyanestrogenreceptoradependentregulationofglucosetransporterfunctionalexpression AT zhejin glucoseabsorptionintheduodenumismodulatedbyanestrogenreceptoradependentregulationofglucosetransporterfunctionalexpression AT mingkaichen glucoseabsorptionintheduodenumismodulatedbyanestrogenreceptoradependentregulationofglucosetransporterfunctionalexpression |