JCI insightApr 6, 2018

17-β Estradiol controls hormone release from mouse and human gut cells involved in blood sugar regulation

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 31, 2026

Abstract

Ovariectomized mice exhibited impaired glucose tolerance, which was reversed by estradiol treatment.

Decreased GLP-1 secretion and content were observed in ovariectomized mice, indicating a link between sexual hormone deprivation and glucose metabolism.
Estradiol treatment restored GLP-1 secretion in both intestinal and pancreatic sources, suggesting a direct effect on hormone-producing cells.
Estradiol increased GLP-1 secretion through activation of all three estrogen receptors in pancreatic α cells.
In intestinal explants, GLP-1 secretion in response to estradiol occurred specifically via activation of the estrogen receptor beta (ERβ).
The selective ERβ agonist WAY20070 improved glucose tolerance in ovariectomized mice, partially through increased plasma GLP-1 levels.

Simplified

Clinical and experimental data indicate a beneficial effect of estrogens on energy and glucose homeostasis associated with improved insulin sensitivity and positive effects on insulin secretion. The aim of the study was to investigate the impact of estrogens on proglucagon-producing cells, pancreatic α cells, and enteroendocrine L cells. The consequences of sexual hormone deprivation were evaluated in ovariectomized mice (ovx). Ovx mice exhibited impaired glucose tolerance during oral glucose tolerance tests (OGTT), which was associated with decreased GLP-1 intestinal and pancreatic secretion and content, an effect that was reversed by estradiol (E2) treatment. Indeed, E2 increased oral glucose-induced GLP-1 secretion in vivo and GLP-1 secretion from primary culture of mouse and human α cells through the activation of all 3 estrogen receptors (ERs), whereas E2-induced GLP-1 secretion from mouse and human intestinal explants occurred only by ERβ activation. Underlying the implication of ERβ, its selective agonist WAY20070 was able to restore glucose tolerance in ovx mice at least partly through plasma GLP-1 increase. We conclude that E2 directly controls both α- and L cells to increase GLP-1 secretion, in addition to its effects on insulin and glucagon secretion, highlighting the potential beneficial role of the estrogenic pathway and, more particularly, of ERβ agonists to prevent type 2 diabetes.

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Conflict of interest: The authors declare that no conflict of interest exists.

PubMed

17-β Estradiol controls hormone release from mouse and human gut cells involved in blood sugar regulation

Abstract

Full Text

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Competing interests

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Abstract

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Funding

Competing interests

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