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Distinct Cell Clusters Touching Islet Cells Induce Islet Cell Replication in Association with Over-Expression of Regenerating Gene (REG) Protein in Fulminant Type 1 Diabetes
BACKGROUND: Pancreatic islet endocrine cell-supporting architectures, including islet encapsulating basement membranes (BMs), extracellular matrix (ECM), and possible cell clusters, are unclear. PROCEDURES: The architectures around islet cell clusters, including BMs, ECM, and pancreatic acinar-like...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997392/ https://www.ncbi.nlm.nih.gov/pubmed/24759849 http://dx.doi.org/10.1371/journal.pone.0095110 |
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author | Aida, Kaoru Saitoh, Sei Nishida, Yoriko Yokota, Sadanori Ohno, Shinichi Mao, Xiayang Akiyama, Daiichiro Tanaka, Shoichiro Awata, Takuya Shimada, Akira Oikawa, Youichi Shimura, Hiroki Furuya, Fumihiko Takizawa, Soichi Ichijo, Masashi Ichijo, Sayaka Itakura, Jun Fujii, Hideki Hashiguchi, Akinori Takasawa, Shin Endo, Toyoshi Kobayashi, Tetsuro |
author_facet | Aida, Kaoru Saitoh, Sei Nishida, Yoriko Yokota, Sadanori Ohno, Shinichi Mao, Xiayang Akiyama, Daiichiro Tanaka, Shoichiro Awata, Takuya Shimada, Akira Oikawa, Youichi Shimura, Hiroki Furuya, Fumihiko Takizawa, Soichi Ichijo, Masashi Ichijo, Sayaka Itakura, Jun Fujii, Hideki Hashiguchi, Akinori Takasawa, Shin Endo, Toyoshi Kobayashi, Tetsuro |
author_sort | Aida, Kaoru |
collection | PubMed |
description | BACKGROUND: Pancreatic islet endocrine cell-supporting architectures, including islet encapsulating basement membranes (BMs), extracellular matrix (ECM), and possible cell clusters, are unclear. PROCEDURES: The architectures around islet cell clusters, including BMs, ECM, and pancreatic acinar-like cell clusters, were studied in the non-diabetic state and in the inflamed milieu of fulminant type 1 diabetes in humans. RESULT: Immunohistochemical and electron microscopy analyses demonstrated that human islet cell clusters and acinar-like cell clusters adhere directly to each other with desmosomal structures and coated-pit-like structures between the two cell clusters. The two cell-clusters are encapsulated by a continuous capsule composed of common BMs/ECM. The acinar-like cell clusters have vesicles containing regenerating (REG) Iα protein. The vesicles containing REG Iα protein are directly secreted to islet cells. In the inflamed milieu of fulminant type 1 diabetes, the acinar-like cell clusters over-expressed REG Iα protein. Islet endocrine cells, including beta-cells and non-beta cells, which were packed with the acinar-like cell clusters, show self-replication with a markedly increased number of Ki67-positive cells. CONCLUSION: The acinar-like cell clusters touching islet endocrine cells are distinct, because the cell clusters are packed with pancreatic islet clusters and surrounded by common BMs/ECM. Furthermore, the acinar-like cell clusters express REG Iα protein and secrete directly to neighboring islet endocrine cells in the non-diabetic state, and the cell clusters over-express REG Iα in the inflamed milieu of fulminant type 1 diabetes with marked self-replication of islet cells. |
format | Online Article Text |
id | pubmed-3997392 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39973922014-04-29 Distinct Cell Clusters Touching Islet Cells Induce Islet Cell Replication in Association with Over-Expression of Regenerating Gene (REG) Protein in Fulminant Type 1 Diabetes Aida, Kaoru Saitoh, Sei Nishida, Yoriko Yokota, Sadanori Ohno, Shinichi Mao, Xiayang Akiyama, Daiichiro Tanaka, Shoichiro Awata, Takuya Shimada, Akira Oikawa, Youichi Shimura, Hiroki Furuya, Fumihiko Takizawa, Soichi Ichijo, Masashi Ichijo, Sayaka Itakura, Jun Fujii, Hideki Hashiguchi, Akinori Takasawa, Shin Endo, Toyoshi Kobayashi, Tetsuro PLoS One Research Article BACKGROUND: Pancreatic islet endocrine cell-supporting architectures, including islet encapsulating basement membranes (BMs), extracellular matrix (ECM), and possible cell clusters, are unclear. PROCEDURES: The architectures around islet cell clusters, including BMs, ECM, and pancreatic acinar-like cell clusters, were studied in the non-diabetic state and in the inflamed milieu of fulminant type 1 diabetes in humans. RESULT: Immunohistochemical and electron microscopy analyses demonstrated that human islet cell clusters and acinar-like cell clusters adhere directly to each other with desmosomal structures and coated-pit-like structures between the two cell clusters. The two cell-clusters are encapsulated by a continuous capsule composed of common BMs/ECM. The acinar-like cell clusters have vesicles containing regenerating (REG) Iα protein. The vesicles containing REG Iα protein are directly secreted to islet cells. In the inflamed milieu of fulminant type 1 diabetes, the acinar-like cell clusters over-expressed REG Iα protein. Islet endocrine cells, including beta-cells and non-beta cells, which were packed with the acinar-like cell clusters, show self-replication with a markedly increased number of Ki67-positive cells. CONCLUSION: The acinar-like cell clusters touching islet endocrine cells are distinct, because the cell clusters are packed with pancreatic islet clusters and surrounded by common BMs/ECM. Furthermore, the acinar-like cell clusters express REG Iα protein and secrete directly to neighboring islet endocrine cells in the non-diabetic state, and the cell clusters over-express REG Iα in the inflamed milieu of fulminant type 1 diabetes with marked self-replication of islet cells. Public Library of Science 2014-04-23 /pmc/articles/PMC3997392/ /pubmed/24759849 http://dx.doi.org/10.1371/journal.pone.0095110 Text en © 2014 Aida 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 Aida, Kaoru Saitoh, Sei Nishida, Yoriko Yokota, Sadanori Ohno, Shinichi Mao, Xiayang Akiyama, Daiichiro Tanaka, Shoichiro Awata, Takuya Shimada, Akira Oikawa, Youichi Shimura, Hiroki Furuya, Fumihiko Takizawa, Soichi Ichijo, Masashi Ichijo, Sayaka Itakura, Jun Fujii, Hideki Hashiguchi, Akinori Takasawa, Shin Endo, Toyoshi Kobayashi, Tetsuro Distinct Cell Clusters Touching Islet Cells Induce Islet Cell Replication in Association with Over-Expression of Regenerating Gene (REG) Protein in Fulminant Type 1 Diabetes |
title | Distinct Cell Clusters Touching Islet Cells Induce Islet Cell Replication in Association with Over-Expression of Regenerating Gene (REG) Protein in Fulminant Type 1 Diabetes |
title_full | Distinct Cell Clusters Touching Islet Cells Induce Islet Cell Replication in Association with Over-Expression of Regenerating Gene (REG) Protein in Fulminant Type 1 Diabetes |
title_fullStr | Distinct Cell Clusters Touching Islet Cells Induce Islet Cell Replication in Association with Over-Expression of Regenerating Gene (REG) Protein in Fulminant Type 1 Diabetes |
title_full_unstemmed | Distinct Cell Clusters Touching Islet Cells Induce Islet Cell Replication in Association with Over-Expression of Regenerating Gene (REG) Protein in Fulminant Type 1 Diabetes |
title_short | Distinct Cell Clusters Touching Islet Cells Induce Islet Cell Replication in Association with Over-Expression of Regenerating Gene (REG) Protein in Fulminant Type 1 Diabetes |
title_sort | distinct cell clusters touching islet cells induce islet cell replication in association with over-expression of regenerating gene (reg) protein in fulminant type 1 diabetes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997392/ https://www.ncbi.nlm.nih.gov/pubmed/24759849 http://dx.doi.org/10.1371/journal.pone.0095110 |
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