TY - JOUR
T1 - Beta-cell dysfunction induced by non-cytotoxic concentrations of Interleukin-1β is associated with changes in expression of beta-cell maturity genes and associated histone modifications
AU - Ibarra Urizar, Adriana
AU - Prause, Michala
AU - Wortham, Matthew
AU - Sui, Yinghui
AU - Thams, Peter
AU - Sander, Maike
AU - Christensen, Gitte Lund
AU - Billestrup, Nils
N1 - Publisher Copyright: © 2019 Elsevier B.V.
PY - 2019/10/1
Y1 - 2019/10/1
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-1β 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-1β 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-1β, 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-1β 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-1β 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-1β 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-1β, 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-1β induces epigenetic changes associated with loss of beta-cell identity as observed in Type 2 diabetes.
KW - disease, health science and nursing
KW - Beta-cell dedifferentiation
KW - Beta-cell dysfunction
KW - Cytokines
KW - Histone modifications
KW - Insulin secretion
KW - Proliferation
UR - http://www.scopus.com/inward/record.url?scp=85071788103&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2019.110524
DO - 10.1016/j.mce.2019.110524
M3 - Review article
C2 - 31362031
SN - 0303-7207
VL - 496
SP - 1
EP - 12
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
M1 - 110524
ER -