The mif gene is transcriptionally regulated by glucose in insulin-secreting cells

Biochem Biophys Res Commun. 2002 Jul 5;295(1):174-81. doi: 10.1016/s0006-291x(02)00648-4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Line
  • DNA-Binding Proteins / metabolism
  • Glucose / pharmacology*
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Macrophage Migration-Inhibitory Factors / biosynthesis
  • Macrophage Migration-Inhibitory Factors / genetics*
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • RNA, Messenger / biosynthesis
  • Transcriptional Activation*


  • DNA-Binding Proteins
  • Insulin
  • Macrophage Migration-Inhibitory Factors
  • RNA, Messenger
  • Glucose