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Sustained Beta-Cell Dysfunction but Normalized Islet Mass in Aged Thrombospondin-1 Deficient Mice
Pancreatic islet endothelial cells have in recent years been shown to support beta-cell mass and function by paracrine interactions. Recently, we identified an islets endothelial-specific glycoprotein, thrombospondin-1 (TSP-1), that showed to be of importance for islet angiogenesis and beta-cell fun...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477147/ https://www.ncbi.nlm.nih.gov/pubmed/23094049 http://dx.doi.org/10.1371/journal.pone.0047451 |
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author | Drott, Carl Johan Olerud, Johan Emanuelsson, Hanna Christoffersson, Gustav Carlsson, Per-Ola |
author_facet | Drott, Carl Johan Olerud, Johan Emanuelsson, Hanna Christoffersson, Gustav Carlsson, Per-Ola |
author_sort | Drott, Carl Johan |
collection | PubMed |
description | Pancreatic islet endothelial cells have in recent years been shown to support beta-cell mass and function by paracrine interactions. Recently, we identified an islets endothelial-specific glycoprotein, thrombospondin-1 (TSP-1), that showed to be of importance for islet angiogenesis and beta-cell function in young mice. The present study aimed to investigate long-term consequences for islet morphology and beta-cell function of TSP-1 deficiency. Islet and beta-cell mass were observed increased at 10–12 weeks of age in TSP-1 deficient mice, but were normalized before 16 weeks of age when compared to wild-type controls. Islet vascularity was normal in 10–12 and 16-week-old TSP-1 deficient animals, whereas islets of one-year-old animals lacking TSP-1 were hypervascular. Beta-cell dysfunction in TSP-1 deficient animals was present at similar magnitudes between 10–12 and 52 weeks of age, as evaluated by glucose tolerance tests. The insulin secretion capacity in vivo of islets in one-year-old TSP-1 deficient animals was only ∼15% of that in wild-type animals. Using a transplantation model, we reconstituted TSP-1 in adult TSP-deficient islets. In contrast to neonatal TSP-1 deficient islets that we previously reported to regain function after TSP-1 reconstitution, adult islets failed to recover. We conclude that TSP-1 deficiency in islets causes changing vascular and endocrine morphological alterations postnatally, but is coupled to a chronic beta-cell dysfunction. The beta-cell dysfunction induced by TSP-1 deficiency is irreversible if not substituted early in life. |
format | Online Article Text |
id | pubmed-3477147 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34771472012-10-23 Sustained Beta-Cell Dysfunction but Normalized Islet Mass in Aged Thrombospondin-1 Deficient Mice Drott, Carl Johan Olerud, Johan Emanuelsson, Hanna Christoffersson, Gustav Carlsson, Per-Ola PLoS One Research Article Pancreatic islet endothelial cells have in recent years been shown to support beta-cell mass and function by paracrine interactions. Recently, we identified an islets endothelial-specific glycoprotein, thrombospondin-1 (TSP-1), that showed to be of importance for islet angiogenesis and beta-cell function in young mice. The present study aimed to investigate long-term consequences for islet morphology and beta-cell function of TSP-1 deficiency. Islet and beta-cell mass were observed increased at 10–12 weeks of age in TSP-1 deficient mice, but were normalized before 16 weeks of age when compared to wild-type controls. Islet vascularity was normal in 10–12 and 16-week-old TSP-1 deficient animals, whereas islets of one-year-old animals lacking TSP-1 were hypervascular. Beta-cell dysfunction in TSP-1 deficient animals was present at similar magnitudes between 10–12 and 52 weeks of age, as evaluated by glucose tolerance tests. The insulin secretion capacity in vivo of islets in one-year-old TSP-1 deficient animals was only ∼15% of that in wild-type animals. Using a transplantation model, we reconstituted TSP-1 in adult TSP-deficient islets. In contrast to neonatal TSP-1 deficient islets that we previously reported to regain function after TSP-1 reconstitution, adult islets failed to recover. We conclude that TSP-1 deficiency in islets causes changing vascular and endocrine morphological alterations postnatally, but is coupled to a chronic beta-cell dysfunction. The beta-cell dysfunction induced by TSP-1 deficiency is irreversible if not substituted early in life. Public Library of Science 2012-10-19 /pmc/articles/PMC3477147/ /pubmed/23094049 http://dx.doi.org/10.1371/journal.pone.0047451 Text en © 2012 Drott et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Drott, Carl Johan Olerud, Johan Emanuelsson, Hanna Christoffersson, Gustav Carlsson, Per-Ola Sustained Beta-Cell Dysfunction but Normalized Islet Mass in Aged Thrombospondin-1 Deficient Mice |
title | Sustained Beta-Cell Dysfunction but Normalized Islet Mass in Aged Thrombospondin-1 Deficient Mice |
title_full | Sustained Beta-Cell Dysfunction but Normalized Islet Mass in Aged Thrombospondin-1 Deficient Mice |
title_fullStr | Sustained Beta-Cell Dysfunction but Normalized Islet Mass in Aged Thrombospondin-1 Deficient Mice |
title_full_unstemmed | Sustained Beta-Cell Dysfunction but Normalized Islet Mass in Aged Thrombospondin-1 Deficient Mice |
title_short | Sustained Beta-Cell Dysfunction but Normalized Islet Mass in Aged Thrombospondin-1 Deficient Mice |
title_sort | sustained beta-cell dysfunction but normalized islet mass in aged thrombospondin-1 deficient mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477147/ https://www.ncbi.nlm.nih.gov/pubmed/23094049 http://dx.doi.org/10.1371/journal.pone.0047451 |
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