Beta cell adaptation to pregnancy requires prolactin action on both beta and non-beta cells

Abstract Pancreatic islets adapt to insulin resistance of pregnancy by up regulating β-cell mass and increasing insulin secretion. Previously, using a transgenic mouse with global, heterozygous deletion of prolactin receptor (Prlr+/−), we found Prlr signaling is important for this adaptation. Howeve...

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Autores principales:	Vipul Shrivastava, Megan Lee, Daniel Lee, Marle Pretorius, Bethany Radford, Guneet Makkar, Carol Huang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0f78478bc028430e997b787afda132c9
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spelling	oai:doaj.org-article:0f78478bc028430e997b787afda132c92021-12-02T17:15:22ZBeta cell adaptation to pregnancy requires prolactin action on both beta and non-beta cells10.1038/s41598-021-89745-92045-2322https://doaj.org/article/0f78478bc028430e997b787afda132c92021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89745-9https://doaj.org/toc/2045-2322Abstract Pancreatic islets adapt to insulin resistance of pregnancy by up regulating β-cell mass and increasing insulin secretion. Previously, using a transgenic mouse with global, heterozygous deletion of prolactin receptor (Prlr+/−), we found Prlr signaling is important for this adaptation. However, since Prlr is expressed in tissues outside of islets as well as within islets and prolactin signaling affects β-cell development, to understand β-cell-specific effect of prolactin signaling in pregnancy, we generated a transgenic mouse with an inducible conditional deletion of Prlr from β-cells. Here, we found that β-cell-specific Prlr reduction in adult mice led to elevated blood glucose, lowed β-cell mass and blunted in vivo glucose-stimulated insulin secretion during pregnancy. When we compared gene expression profile of islets from transgenic mice with global (Prlr+/−) versus β-cell-specific Prlr reduction (βPrlR+/−), we found 95 differentially expressed gene, most of them down regulated in the Prlr+/− mice in comparison to the βPrlR+/− mice, and many of these genes regulate apoptosis, synaptic vesicle function and neuronal development. Importantly, we found that islets from pregnant Prlr+/− mice are more vulnerable to glucolipotoxicity-induced apoptosis than islets from pregnant βPrlR+/− mice. These observations suggest that down regulation of prolactin action during pregnancy in non-β-cells secondarily and negatively affect β-cell gene expression, and increased β-cell susceptibility to external insults.Vipul ShrivastavaMegan LeeDaniel LeeMarle PretoriusBethany RadfordGuneet MakkarCarol HuangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Vipul Shrivastava Megan Lee Daniel Lee Marle Pretorius Bethany Radford Guneet Makkar Carol Huang Beta cell adaptation to pregnancy requires prolactin action on both beta and non-beta cells
description	Abstract Pancreatic islets adapt to insulin resistance of pregnancy by up regulating β-cell mass and increasing insulin secretion. Previously, using a transgenic mouse with global, heterozygous deletion of prolactin receptor (Prlr+/−), we found Prlr signaling is important for this adaptation. However, since Prlr is expressed in tissues outside of islets as well as within islets and prolactin signaling affects β-cell development, to understand β-cell-specific effect of prolactin signaling in pregnancy, we generated a transgenic mouse with an inducible conditional deletion of Prlr from β-cells. Here, we found that β-cell-specific Prlr reduction in adult mice led to elevated blood glucose, lowed β-cell mass and blunted in vivo glucose-stimulated insulin secretion during pregnancy. When we compared gene expression profile of islets from transgenic mice with global (Prlr+/−) versus β-cell-specific Prlr reduction (βPrlR+/−), we found 95 differentially expressed gene, most of them down regulated in the Prlr+/− mice in comparison to the βPrlR+/− mice, and many of these genes regulate apoptosis, synaptic vesicle function and neuronal development. Importantly, we found that islets from pregnant Prlr+/− mice are more vulnerable to glucolipotoxicity-induced apoptosis than islets from pregnant βPrlR+/− mice. These observations suggest that down regulation of prolactin action during pregnancy in non-β-cells secondarily and negatively affect β-cell gene expression, and increased β-cell susceptibility to external insults.
format	article
author	Vipul Shrivastava Megan Lee Daniel Lee Marle Pretorius Bethany Radford Guneet Makkar Carol Huang
author_facet	Vipul Shrivastava Megan Lee Daniel Lee Marle Pretorius Bethany Radford Guneet Makkar Carol Huang
author_sort	Vipul Shrivastava
title	Beta cell adaptation to pregnancy requires prolactin action on both beta and non-beta cells
title_short	Beta cell adaptation to pregnancy requires prolactin action on both beta and non-beta cells
title_full	Beta cell adaptation to pregnancy requires prolactin action on both beta and non-beta cells
title_fullStr	Beta cell adaptation to pregnancy requires prolactin action on both beta and non-beta cells
title_full_unstemmed	Beta cell adaptation to pregnancy requires prolactin action on both beta and non-beta cells
title_sort	beta cell adaptation to pregnancy requires prolactin action on both beta and non-beta cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0f78478bc028430e997b787afda132c9
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Beta cell adaptation to pregnancy requires prolactin action on both beta and non-beta cells

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