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

Kaoru Aida, Sei Saitoh, Yoriko Nishida, Sadanori Yokota, Shinichi Ohno, Xiayang Mao, Daiichiro Akiyama, Shoichiro Tanaka, Takuya Awata, Akira Shimada, Youichi Oikawa, Hiroki Shimura, Fumihiko Furuya, Soichi Takizawa, Masashi Ichijo, Sayaka Ichijo, Jun Itakura, Hideki Fujii, Akinori Hashiguchi, Shin TakasawaToyoshi Endo, Tetsuro Kobayashi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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) Ia protein. The vesicles containing REG Ia protein are directly secreted to islet cells. In the inflamed milieu of fulminant type 1 diabetes, the acinar-like cell clusters over-expressed REG Ia 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 Ia protein and secrete directly to neighboring islet endocrine cells in the non-diabetic state, and the cell clusters over-express REG Ia in the inflamed milieu of fulminant type 1 diabetes with marked self-replication of islet cells.

Original languageEnglish
Article numbere95110
JournalPLoS One
Volume9
Issue number4
DOIs
Publication statusPublished - 2014 Apr 23

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gene overexpression
insulin-dependent diabetes mellitus
islets of Langerhans
Medical problems
Type 1 Diabetes Mellitus
Islets of Langerhans
Acinar Cells
Cells
Genes
Endocrine Cells
Proteins
Basement Membrane
proteins
Extracellular Matrix
cells
basement membrane
extracellular matrix
Electron microscopy
Capsules
Electron Microscopy

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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.

In: PLoS One, Vol. 9, No. 4, e95110, 23.04.2014.

Research output: Contribution to journalArticle

Aida, K, Saitoh, S, Nishida, Y, Yokota, S, Ohno, S, Mao, X, Akiyama, D, Tanaka, S, Awata, T, Shimada, A, Oikawa, Y, Shimura, H, Furuya, F, Takizawa, S, Ichijo, M, Ichijo, S, Itakura, J, Fujii, H, Hashiguchi, A, Takasawa, S, Endo, T & Kobayashi, T 2014, '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', PLoS One, vol. 9, no. 4, e95110. https://doi.org/10.1371/journal.pone.0095110
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. In: PLoS One. 2014 ; Vol. 9, No. 4.
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abstract = "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) Ia protein. The vesicles containing REG Ia protein are directly secreted to islet cells. In the inflamed milieu of fulminant type 1 diabetes, the acinar-like cell clusters over-expressed REG Ia 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 Ia protein and secrete directly to neighboring islet endocrine cells in the non-diabetic state, and the cell clusters over-express REG Ia in the inflamed milieu of fulminant type 1 diabetes with marked self-replication of islet cells.",
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AU - Aida, Kaoru

AU - Saitoh, Sei

AU - Nishida, Yoriko

AU - Yokota, Sadanori

AU - Ohno, Shinichi

AU - Mao, Xiayang

AU - Akiyama, Daiichiro

AU - Tanaka, Shoichiro

AU - Awata, Takuya

AU - Shimada, Akira

AU - Oikawa, Youichi

AU - Shimura, Hiroki

AU - Furuya, Fumihiko

AU - Takizawa, Soichi

AU - Ichijo, Masashi

AU - Ichijo, Sayaka

AU - Itakura, Jun

AU - Fujii, Hideki

AU - Hashiguchi, Akinori

AU - Takasawa, Shin

AU - Endo, Toyoshi

AU - Kobayashi, Tetsuro

PY - 2014/4/23

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