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Milk Exosomal microRNAs: Postnatal Promoters of β Cell Proliferation but Potential Inducers of β Cell De-Differentiation in Adult Life
Pancreatic β cell expansion and functional maturation during the birth-to-weaning period is driven by epigenetic programs primarily triggered by growth factors, hormones, and nutrients provided by human milk. As shown recently, exosomes derived from various origins interact with β cells. This review...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569743/ https://www.ncbi.nlm.nih.gov/pubmed/36232796 http://dx.doi.org/10.3390/ijms231911503 |
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author | Melnik, Bodo C. Schmitz, Gerd |
author_facet | Melnik, Bodo C. Schmitz, Gerd |
author_sort | Melnik, Bodo C. |
collection | PubMed |
description | Pancreatic β cell expansion and functional maturation during the birth-to-weaning period is driven by epigenetic programs primarily triggered by growth factors, hormones, and nutrients provided by human milk. As shown recently, exosomes derived from various origins interact with β cells. This review elucidates the potential role of milk-derived exosomes (MEX) and their microRNAs (miRs) on pancreatic β cell programming during the postnatal period of lactation as well as during continuous cow milk exposure of adult humans to bovine MEX. Mechanistic evidence suggests that MEX miRs stimulate mTORC1/c-MYC-dependent postnatal β cell proliferation and glycolysis, but attenuate β cell differentiation, mitochondrial function, and insulin synthesis and secretion. MEX miR content is negatively affected by maternal obesity, gestational diabetes, psychological stress, caesarean delivery, and is completely absent in infant formula. Weaning-related disappearance of MEX miRs may be the critical event switching β cells from proliferation to TGF-β/AMPK-mediated cell differentiation, whereas continued exposure of adult humans to bovine MEX miRs via intake of pasteurized cow milk may reverse β cell differentiation, promoting β cell de-differentiation. Whereas MEX miR signaling supports postnatal β cell proliferation (diabetes prevention), persistent bovine MEX exposure after the lactation period may de-differentiate β cells back to the postnatal phenotype (diabetes induction). |
format | Online Article Text |
id | pubmed-9569743 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95697432022-10-17 Milk Exosomal microRNAs: Postnatal Promoters of β Cell Proliferation but Potential Inducers of β Cell De-Differentiation in Adult Life Melnik, Bodo C. Schmitz, Gerd Int J Mol Sci Review Pancreatic β cell expansion and functional maturation during the birth-to-weaning period is driven by epigenetic programs primarily triggered by growth factors, hormones, and nutrients provided by human milk. As shown recently, exosomes derived from various origins interact with β cells. This review elucidates the potential role of milk-derived exosomes (MEX) and their microRNAs (miRs) on pancreatic β cell programming during the postnatal period of lactation as well as during continuous cow milk exposure of adult humans to bovine MEX. Mechanistic evidence suggests that MEX miRs stimulate mTORC1/c-MYC-dependent postnatal β cell proliferation and glycolysis, but attenuate β cell differentiation, mitochondrial function, and insulin synthesis and secretion. MEX miR content is negatively affected by maternal obesity, gestational diabetes, psychological stress, caesarean delivery, and is completely absent in infant formula. Weaning-related disappearance of MEX miRs may be the critical event switching β cells from proliferation to TGF-β/AMPK-mediated cell differentiation, whereas continued exposure of adult humans to bovine MEX miRs via intake of pasteurized cow milk may reverse β cell differentiation, promoting β cell de-differentiation. Whereas MEX miR signaling supports postnatal β cell proliferation (diabetes prevention), persistent bovine MEX exposure after the lactation period may de-differentiate β cells back to the postnatal phenotype (diabetes induction). MDPI 2022-09-29 /pmc/articles/PMC9569743/ /pubmed/36232796 http://dx.doi.org/10.3390/ijms231911503 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Melnik, Bodo C. Schmitz, Gerd Milk Exosomal microRNAs: Postnatal Promoters of β Cell Proliferation but Potential Inducers of β Cell De-Differentiation in Adult Life |
title | Milk Exosomal microRNAs: Postnatal Promoters of β Cell Proliferation but Potential Inducers of β Cell De-Differentiation in Adult Life |
title_full | Milk Exosomal microRNAs: Postnatal Promoters of β Cell Proliferation but Potential Inducers of β Cell De-Differentiation in Adult Life |
title_fullStr | Milk Exosomal microRNAs: Postnatal Promoters of β Cell Proliferation but Potential Inducers of β Cell De-Differentiation in Adult Life |
title_full_unstemmed | Milk Exosomal microRNAs: Postnatal Promoters of β Cell Proliferation but Potential Inducers of β Cell De-Differentiation in Adult Life |
title_short | Milk Exosomal microRNAs: Postnatal Promoters of β Cell Proliferation but Potential Inducers of β Cell De-Differentiation in Adult Life |
title_sort | milk exosomal micrornas: postnatal promoters of β cell proliferation but potential inducers of β cell de-differentiation in adult life |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569743/ https://www.ncbi.nlm.nih.gov/pubmed/36232796 http://dx.doi.org/10.3390/ijms231911503 |
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