Tubular complexes as a source for islet neogenesis in the pancreas of diabetes-prone BB rats

• Published in: Laboratory investigation 2005-05, Vol.85 (5), p.675-688
• Main Authors: Wang, Gen-Sheng, Rosenberg, Lawrence, Scott, Fraser W
• Format: Article
• Language: English
• Subjects: Amylases - metabolism; Animals; Apoptosis; Biological and medical sciences; Biomarkers - metabolism; Biotechnology; Cell Differentiation; Cell Proliferation; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - pathology; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; In Situ Nick-End Labeling; Investigative techniques, diagnostic techniques (general aspects); Islets of Langerhans - metabolism; Islets of Langerhans - pathology; Keratins - metabolism; Laboratory Medicine; Medical sciences; Medicine; Medicine & Public Health; Pancreas, Exocrine - metabolism; Pancreas, Exocrine - pathology; Pathology; Rats; Rats, Inbred BB; Rats, Inbred WF; Regeneration; research-article; Stem Cells - metabolism; Stem Cells - pathology; Vimentin - metabolism
• ISSN: 0023-6837; 1530-0307
• DOI: 10.1038/labinvest.3700259

Tubular complexes (TC) in the pancreas contain duct-like structures with low cuboidal or flattened cells surrounding a large lumen and are thought to be a response to pancreatic injury. TC have been studied in animal models of chemical or surgically induced pancreatic damage but their occurrence has not been reported in rodent models of spontaneous autoimmune type I diabetes. We hypothesized that TC would be increased during the active phase of islet destruction in autoimmune diabetes and could contain islet progenitor cells. We analyzed TC in pancreas of Wistar Furth (WF), control (BBc) and diabetes-prone BioBreeding (BBdp) rats using immunohistochemistry and morphometry. TC were observed in all rat strains during active pancreas remodeling (∼13 days). They increased between 60 and 93 days only in BBdp rats coincident with the increase in diabetes cases. Most TC were infiltrated with CD3 + T-cells. Duct-like cells in the TC had low expression of the exocrine marker amylase, increased expression of epithelial cell markers, keratin and vimentin, and remarkably high cell proliferation and cell death. TC islets contained cells stained positive for insulin, glucagon, somatostatin, pancreatic polypeptide, as well as PDX-1, chromogranin, and hepatocyte-derived growth factor receptor, c-met. Transitional cells that were keratin + /insulin + and keratin + /amylase + cells were present in TC. The stem cell marker, nestin was upregulated in the TC region. Duct-like cells in TC of BBdp rats expressed markers of committed endocrine precursors: PDX-1, neurogenin 3 and protein gene product 9.5. This study demonstrates that TC are upregulated during β -cell destruction and contain potential endocrine progenitors.