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17-β Estradiol regulates proglucagon-derived peptide secretion in mouse and human α- and L cells
Sandra Handgraaf, … , Jacques Philippe, Yvan Gosmain
Sandra Handgraaf, … , Jacques Philippe, Yvan Gosmain
Published April 5, 2018
Citation Information: JCI Insight. 2018;3(7):e98569. https://doi.org/10.1172/jci.insight.98569.
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Research Article Endocrinology Metabolism

17-β Estradiol regulates proglucagon-derived peptide secretion in mouse and human α- and L cells

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Abstract

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.

Authors

Sandra Handgraaf, Rodolphe Dusaulcy, Florian Visentin, Jacques Philippe, Yvan Gosmain

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Figure 1

Ovariectomized female mice develop glucose intolerance.

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Ovariectomized female mice develop glucose intolerance.
Plasma glucose l...
Plasma glucose levels during OGTT (2 g/kg) (A) and the related AUCs (B) in sham (gray bars, n = 12) and ovx (white bars, n = 13) mice, 1 week after the surgery. Plasma insulin (C), glucagon (n = 6 at least per group) (D), and GLP-1 levels 5 minutes after gavage (sham, n = 5; ovx, n = 3) (E) during the OGTT. One-way repeated ANOVA with Bonferonni post hoc test analyses were performed for glycemia (A), and 2-tailed Student’s t test statistical analyses were performed for the other results. *P ≤ 0.05 for sham vs. ovx mice.

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