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- Title
Pro-Inflammatory Cytokines Induce Insulin and Glucagon Double Positive Human Islet Cells That Are Resistant to Apoptosis.
- Authors
Tesi, Marta; Bugliani, Marco; Ferri, Gianmarco; Suleiman, Mara; De Luca, Carmela; Bosi, Emanuele; Masini, Matilde; De Tata, Vincenzo; Gysemans, Conny; Cardarelli, Francesco; Cnop, Miriam; Eizirik, Decio L.; Marchetti, Piero; Marselli, Lorella
- Abstract
The presence of islet cells double positive for insulin and glucagon (Ins+/Glu+) has been described in the pancreas from both type 2 (T2D) and type 1 (T1D) diabetic subjects. We studied the role of pro-inflammatory cytokines on the occurrence, trajectory, and characteristics of Ins+/Glu+ cells in human pancreatic islets. Pancreas samples, isolated islets, and dispersed islet cells from 3 T1D and 11 non-diabetic (ND) multi-organ donors were studied by immunofluorescence, confocal microscopy, and/or electron microscopy. ND islet cells were exposed to interleukin-1β and interferon-γ for up to 120 h. In T1D islets, we confirmed an increased prevalence of Ins+/Glu+ cells. Cytokine-exposed islets showed a progressive increase of Ins+/Glu+ cells that represented around 50% of endocrine cells after 120h. Concomitantly, cells expressing insulin granules only decreased significantly over time, whereas those containing only glucagon granules remained stable. Interestingly, Ins+/Glu+ cells were less prone to cytokine-induced apoptosis than cells containing only insulin. Cytokine-exposed islets showed down-regulation of β-cell identity genes. In conclusion, pro-inflammatory cytokines induce Ins+/Glu+ cells in human islets, possibly due to a switch from a β- to a β-/α-cell phenotype. These Ins+/Glu+ cells appear to be resistant to cytokine-induced apoptosis.
- Subjects
GLUCAGON; INSULIN; ISLANDS of Langerhans; CYTOKINES; PANCREAS; CONFOCAL microscopy; ISLANDS; APOPTOSIS
- Publication
Biomolecules (2218-273X), 2021, Vol 11, Issue 2, p320
- ISSN
2218-273X
- Publication type
Article
- DOI
10.3390/biom11020320