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β Cell mass expansion during puberty involves serotonin signaling and determines glucose homeostasis in adulthood

Puberty is associated with transient insulin resistance that normally recedes at the end of puberty; however, in overweight children, insulin resistance persists, leading to an increased risk of type 2 diabetes. The mechanisms whereby pancreatic β cells adapt to pubertal insulin resistance, and how...

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Autores principales: Castell, Anne-Laure, Goubault, Clara, Ethier, Mélanie, Fergusson, Grace, Tremblay, Caroline, Baltz, Marie, Dal Soglio, Dorothée, Ghislain, Julien, Poitout, Vincent
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9675460/
https://www.ncbi.nlm.nih.gov/pubmed/36107617
http://dx.doi.org/10.1172/jci.insight.160854
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author Castell, Anne-Laure
Goubault, Clara
Ethier, Mélanie
Fergusson, Grace
Tremblay, Caroline
Baltz, Marie
Dal Soglio, Dorothée
Ghislain, Julien
Poitout, Vincent
author_facet Castell, Anne-Laure
Goubault, Clara
Ethier, Mélanie
Fergusson, Grace
Tremblay, Caroline
Baltz, Marie
Dal Soglio, Dorothée
Ghislain, Julien
Poitout, Vincent
author_sort Castell, Anne-Laure
collection PubMed
description Puberty is associated with transient insulin resistance that normally recedes at the end of puberty; however, in overweight children, insulin resistance persists, leading to an increased risk of type 2 diabetes. The mechanisms whereby pancreatic β cells adapt to pubertal insulin resistance, and how they are affected by the metabolic status, have not been investigated. Here, we show that puberty is associated with a transient increase in β cell proliferation in rats and humans of both sexes. In rats, β cell proliferation correlated with a rise in growth hormone (GH) levels. Serum from pubertal rats and humans promoted β cell proliferation, suggesting the implication of a circulating factor. In pubertal rat islets, expression of genes of the GH/serotonin (5-hydroxytryptamine [5-HT]) pathway underwent changes consistent with a proliferative effect. Inhibition of the pro-proliferative 5-HT receptor isoform HTR2B blocked the increase in β cell proliferation in pubertal islets ex vivo and in vivo. Peripubertal metabolic stress blunted β cell proliferation during puberty and led to altered glucose homeostasis later in life. This study identifies a role of GH/GH receptor/5-HT/HTR2B signaling in the control of β cell mass expansion during puberty and identifies a mechanistic link between pubertal obesity and the risk of developing type 2 diabetes.
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spelling pubmed-96754602022-11-21 β Cell mass expansion during puberty involves serotonin signaling and determines glucose homeostasis in adulthood Castell, Anne-Laure Goubault, Clara Ethier, Mélanie Fergusson, Grace Tremblay, Caroline Baltz, Marie Dal Soglio, Dorothée Ghislain, Julien Poitout, Vincent JCI Insight Research Article Puberty is associated with transient insulin resistance that normally recedes at the end of puberty; however, in overweight children, insulin resistance persists, leading to an increased risk of type 2 diabetes. The mechanisms whereby pancreatic β cells adapt to pubertal insulin resistance, and how they are affected by the metabolic status, have not been investigated. Here, we show that puberty is associated with a transient increase in β cell proliferation in rats and humans of both sexes. In rats, β cell proliferation correlated with a rise in growth hormone (GH) levels. Serum from pubertal rats and humans promoted β cell proliferation, suggesting the implication of a circulating factor. In pubertal rat islets, expression of genes of the GH/serotonin (5-hydroxytryptamine [5-HT]) pathway underwent changes consistent with a proliferative effect. Inhibition of the pro-proliferative 5-HT receptor isoform HTR2B blocked the increase in β cell proliferation in pubertal islets ex vivo and in vivo. Peripubertal metabolic stress blunted β cell proliferation during puberty and led to altered glucose homeostasis later in life. This study identifies a role of GH/GH receptor/5-HT/HTR2B signaling in the control of β cell mass expansion during puberty and identifies a mechanistic link between pubertal obesity and the risk of developing type 2 diabetes. American Society for Clinical Investigation 2022-11-08 /pmc/articles/PMC9675460/ /pubmed/36107617 http://dx.doi.org/10.1172/jci.insight.160854 Text en © 2022 Castell et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Castell, Anne-Laure
Goubault, Clara
Ethier, Mélanie
Fergusson, Grace
Tremblay, Caroline
Baltz, Marie
Dal Soglio, Dorothée
Ghislain, Julien
Poitout, Vincent
β Cell mass expansion during puberty involves serotonin signaling and determines glucose homeostasis in adulthood
title β Cell mass expansion during puberty involves serotonin signaling and determines glucose homeostasis in adulthood
title_full β Cell mass expansion during puberty involves serotonin signaling and determines glucose homeostasis in adulthood
title_fullStr β Cell mass expansion during puberty involves serotonin signaling and determines glucose homeostasis in adulthood
title_full_unstemmed β Cell mass expansion during puberty involves serotonin signaling and determines glucose homeostasis in adulthood
title_short β Cell mass expansion during puberty involves serotonin signaling and determines glucose homeostasis in adulthood
title_sort β cell mass expansion during puberty involves serotonin signaling and determines glucose homeostasis in adulthood
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9675460/
https://www.ncbi.nlm.nih.gov/pubmed/36107617
http://dx.doi.org/10.1172/jci.insight.160854
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