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bioRxiv · 10.1101/2022.04.06.487366

Beta-cell mass expansion during puberty involves serotonin signaling and determines glucose homeostasis in adulthood

Castell, A.-L.·Ethier, M.·Fergusson, G.·Tremblay, C.·Goubault, C.·Baltz, M.·Dal Soglio, D.·Ghislain, J.·Poitout, V.
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Abstract

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 {beta} 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 {beta}-cell proliferation in rats and humans of both sexes. In rats, {beta}-cell proliferation correlated with a rise in growth hormone (GH) levels. Serum from pubertal rats and humans promoted {beta}-cell proliferation, suggesting the implication of a circulating factor. In pubertal rat islets, expression of genes of the GH/serotonin (5-HT) pathway underwent changes consistent with proliferative effect. Inhibition of the pro-proliferative 5-HT receptor isoform HTR2b blocked the increase in {beta}-cell proliferation in pubertal islets ex vivo and in vivo. Peri-pubertal metabolic stress blunted {beta}-cell proliferation during puberty and led to altered glucose homeostasis later in life. This study identifies a role of GH/GHR/5-HT/HTR2b signaling in the control of {beta}-cell mass expansion during puberty and a mechanistic link between pubertal obesity and the risk of developing type 2 diabetes.

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Castell, A.-L., Ethier, M., Fergusson, G., Tremblay, C., Goubault, C., Baltz, M., Dal Soglio, D., Ghislain, J., Poitout, V.. 2022-04-09. Beta-cell mass expansion during puberty involves serotonin signaling and determines glucose homeostasis in adulthood. https://doi.org/10.1101/2022.04.06.487366

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