Article: article from journal or magazin.
The mif gene is transcriptionally regulated by glucose in insulin-secreting cells.
Biochemical and biophysical research communications
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Macrophage migration inhibitory factor (MIF) is an important regulator of glucose homeostasis. In pancreatic beta-cells, MIF expression is regulated by glucose and its secretion potentiates the glucose-induced insulin secretion. The molecular mechanisms by which glucose mediates its effect on MIF expression are not elucidated. Herein, we report that incubating the differentiated insulin-secreting cell line INS-1 in high glucose concentration increases MIF transcriptional activity as well as the reporter gene activity driven by the -1033 to +63 bp fragment of the MIF promoter. A minimal region located between -187 and -98 bp of this promoter sequence contributes both to basal activity and glucose-responsiveness of the gene. Within this promoter region, two cis-binding sequences were identified by mobility shift assays and footprinting experiments. Both cis-elements interact with nuclear proteins expressed specifically in insulin-secreting cells. In conclusion, we identified a minimal region of the MIF promoter which contributes to the glucose stimulation of the mif gene in insulin-secreting cells.
Animals, Base Sequence, Binding Sites, Cell Line, DNA-Binding Proteins, Glucose, Insulin, Islets of Langerhans, Macrophage Migration-Inhibitory Factors, Molecular Sequence Data, Promoter Regions, Genetic, RNA, Messenger, Transcriptional Activation
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