Co-localization of acinar markers and insulin in pancreatic cells of subjects with type 2 diabetes

• Published in: PloS one Vol. 12; no. 6; p. e0179398
• Main Authors: Masini, Matilde, Marselli, Lorella, Himpe, Eddy, Martino, Luisa, Bugliani, Marco, Suleiman, Mara, Boggi, Ugo, Filipponi, Franco, Occhipinti, Margherita, Bouwens, Luc, De Tata, Vincenzo, Marchetti, Piero
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15.06.2017; Public Library of Science (PLoS)
• Subjects: Aged; Amylases; Beta cells; Biology and Life Sciences; Biomarkers - metabolism; Carboxypeptidase A; Conversion; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Electron microscopy; Enzymes; Female; Gene expression; Granular materials; Granules; Humans; Immune system; Immunofluorescence; Innate immunity; Insulin; Insulin - metabolism; Labels; Laboratories; Light microscopy; Localization; Macrophages; Male; Markers; Marking; Mast cells; Medicine; Medicine and Health Sciences; Middle Aged; Pancreas; Pancreas transplantation; Pancreas, Exocrine - metabolism; Pancreas, Exocrine - ultrastructure; Pancreatic beta cells; Patients; Physiological aspects; Proenzymes; Research and Analysis Methods; Rodents; Searching; Stem cells; Studies; Surgery; Type 2 diabetes
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0179398

To search for clues suggesting that beta cells may generate by transdifferentiation in humans, we assessed the presence of cells double positive for exocrine (amylase, carboxypeptidase A) and endocrine (insulin) markers in the pancreas of non-diabetic individuals (ND) and patients with type 2 diabetes (T2D). Samples from twelve ND and twelve matched T2D multiorgan donors were studied by electron microscopy, including amylase and insulin immunogold labeling; carboxypeptidase A immunofluorescence light microscopy assessment was also performed. In the pancreas from four T2D donors, cells containing both zymogen-like and insulin-like granules were observed, scattered in the exocrine compartment. Nature of granules was confirmed by immunogold labeling for amylase and insulin. Double positive cells ranged from 0.82 to 1.74 per mm2, corresponding to 0.26±0.045% of the counted exocrine cells. Intriguingly, cells of the innate immune systems (mast cells and/or macrophages) were adjacent to 33.3±13.6% of these hybrid cells. No cells showing co-localization of amylase and insulin were found in ND samples by electron microscopy. Similarly, cells containing both carboxypeptidase A and insulin were more frequently observed in the diabetic pancreata. These results demonstrate more abundant presence of cells containing both acinar markers and insulin in the pancreas of T2D subjects, which suggests possible conversion from one cellular type to the other and specific association with the diseased condition.