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
Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt
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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. / Urizar, Adriana Ibarra; Prause, Michala; Wortham, Matthew; Sui, Yinghui; Thams, Peter; Sander, Maike; Christensen, Gitte Lund; Billestrup, Nils.
I: Molecular and Cellular Endocrinology, Bind 496, 110524 , 2019.Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt
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TY - JOUR
T1 - 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
AU - Urizar, Adriana Ibarra
AU - Prause, Michala
AU - Wortham, Matthew
AU - Sui, Yinghui
AU - Thams, Peter
AU - Sander, Maike
AU - Christensen, Gitte Lund
AU - Billestrup, Nils
PY - 2019
Y1 - 2019
N2 - 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
AB - 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
KW - Beta-cell dysfunction
KW - Histone modifications
KW - Beta-cell dedifferentiation
KW - Cytokines
KW - Proliferation
KW - Insulin secretion
U2 - 10.1016/j.mce.2019.110524
DO - 10.1016/j.mce.2019.110524
M3 - Review
C2 - 31362031
VL - 496
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
SN - 0303-7207
M1 - 110524
ER -
ID: 228452365