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Global Deletion of the Prolactin Receptor Aggravates Streptozotocin-Induced Diabetes in Mice
Prolactin (PRL) levels are reduced in the circulation of rats with diabetes or obesity, and lower circulating levels of PRL correlate with increased prevalence of diabetes and a higher risk of metabolic alterations in the clinic. Furthermore, PRL stimulates β-cell proliferation, survival, and insuli...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973366/ https://www.ncbi.nlm.nih.gov/pubmed/33746901 http://dx.doi.org/10.3389/fendo.2021.619696 |
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author | Ramirez-Hernandez, Gabriela Adan-Castro, Elva Diaz-Lezama, Nundehui Ruiz-Herrera, Xarubet Martinez de la Escalera, Gonzalo Macotela, Yazmin Clapp, Carmen |
author_facet | Ramirez-Hernandez, Gabriela Adan-Castro, Elva Diaz-Lezama, Nundehui Ruiz-Herrera, Xarubet Martinez de la Escalera, Gonzalo Macotela, Yazmin Clapp, Carmen |
author_sort | Ramirez-Hernandez, Gabriela |
collection | PubMed |
description | Prolactin (PRL) levels are reduced in the circulation of rats with diabetes or obesity, and lower circulating levels of PRL correlate with increased prevalence of diabetes and a higher risk of metabolic alterations in the clinic. Furthermore, PRL stimulates β-cell proliferation, survival, and insulin production and pregnant mice lacking PRL receptors in β-cells develop gestational diabetes. To investigate the protective effect of endogenous PRL against diabetes outside pregnancy, we compared the number of cases and severity of streptozotocin (STZ)-induced hyperglycemia between C57BL/6 mice null for the PRL receptor gene (Prlr(-/-)) and wild-type mice (Prlr(+/+)). STZ-treated diabetic Prlr(-/-) mice showed a higher number of cases and later recovery from hyperglycemia, exacerbated glucose levels, and glucose intolerance compared to the Prlr(+/+) mice counterparts. Consistent with the worsening of hyperglycemia, pancreatic islet density, β-cell number, proliferation, and survival, as well as circulating insulin levels were reduced, whereas α-cell number and pancreatic inflammation were increased in the absence of PRL signaling. Deletion of the PRL receptor did not alter the metabolic parameters in vehicle-treated animals. We conclude that PRL protects whole body glucose homeostasis by reducing β-cell loss and pancreatic inflammation in STZ-induced diabetes. Medications elevating PRL circulating levels may prove to be beneficial in diabetes. |
format | Online Article Text |
id | pubmed-7973366 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79733662021-03-20 Global Deletion of the Prolactin Receptor Aggravates Streptozotocin-Induced Diabetes in Mice Ramirez-Hernandez, Gabriela Adan-Castro, Elva Diaz-Lezama, Nundehui Ruiz-Herrera, Xarubet Martinez de la Escalera, Gonzalo Macotela, Yazmin Clapp, Carmen Front Endocrinol (Lausanne) Endocrinology Prolactin (PRL) levels are reduced in the circulation of rats with diabetes or obesity, and lower circulating levels of PRL correlate with increased prevalence of diabetes and a higher risk of metabolic alterations in the clinic. Furthermore, PRL stimulates β-cell proliferation, survival, and insulin production and pregnant mice lacking PRL receptors in β-cells develop gestational diabetes. To investigate the protective effect of endogenous PRL against diabetes outside pregnancy, we compared the number of cases and severity of streptozotocin (STZ)-induced hyperglycemia between C57BL/6 mice null for the PRL receptor gene (Prlr(-/-)) and wild-type mice (Prlr(+/+)). STZ-treated diabetic Prlr(-/-) mice showed a higher number of cases and later recovery from hyperglycemia, exacerbated glucose levels, and glucose intolerance compared to the Prlr(+/+) mice counterparts. Consistent with the worsening of hyperglycemia, pancreatic islet density, β-cell number, proliferation, and survival, as well as circulating insulin levels were reduced, whereas α-cell number and pancreatic inflammation were increased in the absence of PRL signaling. Deletion of the PRL receptor did not alter the metabolic parameters in vehicle-treated animals. We conclude that PRL protects whole body glucose homeostasis by reducing β-cell loss and pancreatic inflammation in STZ-induced diabetes. Medications elevating PRL circulating levels may prove to be beneficial in diabetes. Frontiers Media S.A. 2021-03-05 /pmc/articles/PMC7973366/ /pubmed/33746901 http://dx.doi.org/10.3389/fendo.2021.619696 Text en Copyright © 2021 Ramirez-Hernandez, Adan-Castro, Diaz-Lezama, Ruiz-Herrera, Martinez de la Escalera, Macotela and Clapp http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Endocrinology Ramirez-Hernandez, Gabriela Adan-Castro, Elva Diaz-Lezama, Nundehui Ruiz-Herrera, Xarubet Martinez de la Escalera, Gonzalo Macotela, Yazmin Clapp, Carmen Global Deletion of the Prolactin Receptor Aggravates Streptozotocin-Induced Diabetes in Mice |
title | Global Deletion of the Prolactin Receptor Aggravates Streptozotocin-Induced Diabetes in Mice |
title_full | Global Deletion of the Prolactin Receptor Aggravates Streptozotocin-Induced Diabetes in Mice |
title_fullStr | Global Deletion of the Prolactin Receptor Aggravates Streptozotocin-Induced Diabetes in Mice |
title_full_unstemmed | Global Deletion of the Prolactin Receptor Aggravates Streptozotocin-Induced Diabetes in Mice |
title_short | Global Deletion of the Prolactin Receptor Aggravates Streptozotocin-Induced Diabetes in Mice |
title_sort | global deletion of the prolactin receptor aggravates streptozotocin-induced diabetes in mice |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973366/ https://www.ncbi.nlm.nih.gov/pubmed/33746901 http://dx.doi.org/10.3389/fendo.2021.619696 |
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