Cargando…

Nutrient Excess Stimulates β-Cell Neogenesis in Zebrafish

Persistent nutrient excess results in a compensatory increase in the β-cell number in mammals. It is unknown whether this response occurs in nonmammalian vertebrates, including zebrafish, a model for genetics and chemical genetics. We investigated the response of zebrafish β-cells to nutrient excess...

Descripción completa

Detalles Bibliográficos
Autores principales: Maddison, Lisette A., Chen, Wenbiao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3447891/
https://www.ncbi.nlm.nih.gov/pubmed/22721970
http://dx.doi.org/10.2337/db11-1841
_version_ 1782244188066152448
author Maddison, Lisette A.
Chen, Wenbiao
author_facet Maddison, Lisette A.
Chen, Wenbiao
author_sort Maddison, Lisette A.
collection PubMed
description Persistent nutrient excess results in a compensatory increase in the β-cell number in mammals. It is unknown whether this response occurs in nonmammalian vertebrates, including zebrafish, a model for genetics and chemical genetics. We investigated the response of zebrafish β-cells to nutrient excess and the underlying mechanisms by culturing transgenic zebrafish larvae in solutions of different nutrient composition. The number of β-cells rapidly increases after persistent, but not intermittent, exposure to glucose or a lipid-rich diet. The response to glucose, but not the lipid-rich diet, required mammalian target of rapamycin activity. In contrast, inhibition of insulin/IGF-1 signaling in β-cells blocked the response to the lipid-rich diet, but not to glucose. Lineage tracing and marker expression analyses indicated that the new β-cells were not from self-replication but arose through differentiation of postmitotic precursor cells. On the basis of transgenic markers, we identified two groups of newly formed β-cells: one with nkx2.2 promoter activity and the other with mnx1 promoter activity. Thus, nutrient excess in zebrafish induces a rapid increase in β-cells though differentiation of two subpopulations of postmitotic precursor cells. This occurs through different mechanisms depending on the nutrient type and likely involves paracrine signaling between the differentiated β-cells and the precursor cells.
format Online
Article
Text
id pubmed-3447891
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher American Diabetes Association
record_format MEDLINE/PubMed
spelling pubmed-34478912013-10-01 Nutrient Excess Stimulates β-Cell Neogenesis in Zebrafish Maddison, Lisette A. Chen, Wenbiao Diabetes Islet Studies Persistent nutrient excess results in a compensatory increase in the β-cell number in mammals. It is unknown whether this response occurs in nonmammalian vertebrates, including zebrafish, a model for genetics and chemical genetics. We investigated the response of zebrafish β-cells to nutrient excess and the underlying mechanisms by culturing transgenic zebrafish larvae in solutions of different nutrient composition. The number of β-cells rapidly increases after persistent, but not intermittent, exposure to glucose or a lipid-rich diet. The response to glucose, but not the lipid-rich diet, required mammalian target of rapamycin activity. In contrast, inhibition of insulin/IGF-1 signaling in β-cells blocked the response to the lipid-rich diet, but not to glucose. Lineage tracing and marker expression analyses indicated that the new β-cells were not from self-replication but arose through differentiation of postmitotic precursor cells. On the basis of transgenic markers, we identified two groups of newly formed β-cells: one with nkx2.2 promoter activity and the other with mnx1 promoter activity. Thus, nutrient excess in zebrafish induces a rapid increase in β-cells though differentiation of two subpopulations of postmitotic precursor cells. This occurs through different mechanisms depending on the nutrient type and likely involves paracrine signaling between the differentiated β-cells and the precursor cells. American Diabetes Association 2012-10 2012-09-13 /pmc/articles/PMC3447891/ /pubmed/22721970 http://dx.doi.org/10.2337/db11-1841 Text en © 2012 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Islet Studies
Maddison, Lisette A.
Chen, Wenbiao
Nutrient Excess Stimulates β-Cell Neogenesis in Zebrafish
title Nutrient Excess Stimulates β-Cell Neogenesis in Zebrafish
title_full Nutrient Excess Stimulates β-Cell Neogenesis in Zebrafish
title_fullStr Nutrient Excess Stimulates β-Cell Neogenesis in Zebrafish
title_full_unstemmed Nutrient Excess Stimulates β-Cell Neogenesis in Zebrafish
title_short Nutrient Excess Stimulates β-Cell Neogenesis in Zebrafish
title_sort nutrient excess stimulates β-cell neogenesis in zebrafish
topic Islet Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3447891/
https://www.ncbi.nlm.nih.gov/pubmed/22721970
http://dx.doi.org/10.2337/db11-1841
work_keys_str_mv AT maddisonlisettea nutrientexcessstimulatesbcellneogenesisinzebrafish
AT chenwenbiao nutrientexcessstimulatesbcellneogenesisinzebrafish