Beta-cell dysfunction induced by non-cytotoxic concentrations of Interleukin-1 beta is associated with changes in expression of beta-cell maturity genes and associated histone modifications
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Decreased insulin secretory capacity in Type 2 diabetes mellitus is associated with beta-cell dedifferentiation and inflammation. We hypothesize that prolonged exposure of beta-cells to low concentrations of IL-1 beta induce beta-cell dedifferentiation characterized by impaired glucose-stimulated insulin secretion, reduced expression of key beta-cell genes and changes in histone modifications at gene loci known to affect beta-cell function.
Ten days exposure to IL-1 beta at non-cytotoxic concentrations reduced insulin secretion and beta-cell proliferation and decreased expression of key beta-cell identity genes, including MafA and Ucn3 and decreased H3K27ac at the gene loci, suggesting that inflammatory cytokines directly affects the epigenome. Following removal of IL-1 beta, beta-cell function was normalized and mRNA expression of beta-cell identity genes, such as insulin and Ucn3 returned to pre-stimulation levels.
Our findings indicate that prolonged exposure to low concentrations of IL-1 beta induces epigenetic changes associated with loss of beta-cell identity as observed in Type 2 diabetes
Ten days exposure to IL-1 beta at non-cytotoxic concentrations reduced insulin secretion and beta-cell proliferation and decreased expression of key beta-cell identity genes, including MafA and Ucn3 and decreased H3K27ac at the gene loci, suggesting that inflammatory cytokines directly affects the epigenome. Following removal of IL-1 beta, beta-cell function was normalized and mRNA expression of beta-cell identity genes, such as insulin and Ucn3 returned to pre-stimulation levels.
Our findings indicate that prolonged exposure to low concentrations of IL-1 beta induces epigenetic changes associated with loss of beta-cell identity as observed in Type 2 diabetes
Original language | English |
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Article number | 110524 |
Journal | Molecular and Cellular Endocrinology |
Volume | 496 |
Number of pages | 12 |
ISSN | 0303-7207 |
DOIs | |
Publication status | Published - 2019 |
- Beta-cell dysfunction, Histone modifications, Beta-cell dedifferentiation, Cytokines, Proliferation, Insulin secretion
Research areas
ID: 228452365