IBRI RESEARCH PUBLISHED: Pro-Inflammatory Cytokines Induce Insulin and Glucagon Double Positive Human Islet Cells That Are Resistant to Apoptosis

February 19, 2021


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+/Glucells 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+/Glucells. Cytokine-exposed islets showed a progressive increase of Ins+/Glucells 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+/Glucells 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+/Glucells in human islets, possibly due to a switch from a β- to a β-/α-cell phenotype. These Ins+/Glucells appear to be resistant to cytokine-induced apoptosis.

To read the complete research article, go to Biomolecules.