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

• Published in: PloS one 2014-04, Vol.9 (4), p.e95110-e95110
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Analysis; Basement membranes; Beta cells; Biology and Life Sciences; Care and treatment; Cell death; Cluster analysis; Cytokines; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - pathology; Diagnosis; Electron microscopy; Encapsulation; Engineering; Extracellular matrix; Gene expression; Histology; Humans; Inflammation; Interdisciplinary aspects; Internal medicine; Islet cells; Islets of Langerhans; Islets of Langerhans - metabolism; Islets of Langerhans - pathology; Lithostathine - metabolism; Male; Medicine; Medicine and Health Sciences; Membranes; Microscopy, Electron, Transmission; Middle Aged; Overexpression; Pancreas; Pancreas - metabolism; Pancreas - pathology; Pancreatitis; Proteins; Replication; Risk factors; Rodents; Surgery; Topography; Type 1 diabetes; Vesicles
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0095110

Pancreatic islet endocrine cell-supporting architectures, including islet encapsulating basement membranes (BMs), extracellular matrix (ECM), and possible cell clusters, are unclear. 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. 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. 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.