The mif gene is transcriptionally regulated by glucose in insulin-secreting cells.
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.
Plaisance
Valérie
V
Department of Internal Medicine and Institute of Cellular Biology and Morphology, University of Lausanne, Lausanne CH-1011, Switzerland
Thompson
Nancy
N
Niederhauser
Guy
G
Haefliger
Jacques-Antoine
JA
Nicod
Pascal
P
Waeber
Gérard
G
Abderrahmani
Amar
A
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D007328:Insulin; D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D005947:Glucose