2015
DOI: 10.2337/db14-1798
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Estrogen Receptor α Regulates β-Cell Formation During Pancreas Development and Following Injury

Abstract: Identifying pathways for b-cell generation is essential for cell therapy in diabetes. We investigated the potential of 17b-estradiol (E 2 ) and estrogen receptor (ER) signaling for stimulating b-cell generation during embryonic development and in the severely injured adult pancreas. E 2 concentration, ER activity, and number of ERa transcripts were enhanced in the pancreas injured by partial duct ligation (PDL) along with nuclear localization of ERa in b-cells. PDL-induced proliferation of b-cells depended on … Show more

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Cited by 57 publications
(59 citation statements)
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“…They can also derive from neogenesis via a NGN3+ stage [48]. Treatment with the ERα antagonist tamoxifen or genetic elimination of ERα in male mice similarly decreased NGN3 expression and β-cell proliferation in the PDL model, suggesting that ERα is involved in this process [49]. PDL increased E2 in the ligated portion of the pancreas and stimulated nuclear localization of ERα in β-cells (ERα is cytosolic β-cells under normal conditions).…”
Section: Role Of Estrogensmentioning
confidence: 99%
See 1 more Smart Citation
“…They can also derive from neogenesis via a NGN3+ stage [48]. Treatment with the ERα antagonist tamoxifen or genetic elimination of ERα in male mice similarly decreased NGN3 expression and β-cell proliferation in the PDL model, suggesting that ERα is involved in this process [49]. PDL increased E2 in the ligated portion of the pancreas and stimulated nuclear localization of ERα in β-cells (ERα is cytosolic β-cells under normal conditions).…”
Section: Role Of Estrogensmentioning
confidence: 99%
“…PDL increased E2 in the ligated portion of the pancreas and stimulated nuclear localization of ERα in β-cells (ERα is cytosolic β-cells under normal conditions). ERα inhibition with tamoxifen in the embryonic pancreas, or its deletion as in the ERα-deficient mouse, also decreased NGN3 expression and NGN3+ progenitors at the end of gestation [49]. Thus, the generation of NGN3+ cells and the subsequent β-cell mass expansion in developing or injured mouse pancreas are both stimulated by ERα [49].…”
Section: Role Of Estrogensmentioning
confidence: 99%
“…Estradiol increases insulin gene expression and insulin content in β-cells (59,79), increases β-cell proliferation during pancreatic development and recovery from injury (80), and prevents apoptosis of β-cells upon inflammatory insult (59) via ERα- and ERβ-mediated pathways.…”
Section: Extra-gonadal Sites Of Estrogen Synthesis and Its Local Rolesmentioning
confidence: 99%
“…For example, in wild-type female mice, tamoxifen reversed the protective effect of estradiol on preventing insulin-deficient diabetes induced by streptozotocin (STZ), suggesting that tamoxifen acts as an ER antagonist in pancreatic β cells and impairs pancreatic islet survival [20]. In addition, tamoxifen impairs embryonic and adult mouse β-cell proliferation by antagonism of ERα [21]. Treatment with tamoxifen or genetic elimination of ERα in male mice similarly decreased the expression of the endocrine specification factor Neurogenin3 (NGN3) and β-cell proliferation in the partial duct ligation (PDL) rodent model of β-cell expansion due to pancreatic injury.…”
Section: The Effects Of Serms On Glucose Homeostasis and Diabetesmentioning
confidence: 99%
“…Treatment with tamoxifen or genetic elimination of ERα in male mice similarly decreased the expression of the endocrine specification factor Neurogenin3 (NGN3) and β-cell proliferation in the partial duct ligation (PDL) rodent model of β-cell expansion due to pancreatic injury. Further, ERα inhibition with tamoxifen in the embryonic mouse pancreas, or its deletion as in the ERα-deficient mouse, also decreased NGN3 expression and NGN3+ progenitors at the end of gestation [21]. Thus, the generation of NGN3+ cells and the subsequent β-cell mass expansion in developing or injured mouse pancreas are both blocked by tamoxifen antagonizing ERα.…”
Section: The Effects Of Serms On Glucose Homeostasis and Diabetesmentioning
confidence: 99%