Expression, signaling and function of Egr transcription factors in pancreatic β-cells and insulin-responsive tissues

Egr-1 and the related zinc finger transcription factors Egr-2, Egr-3, and Egr-4 are stimulated by many extracellular signaling molecules and represent a convergence point for intracellular signaling cascades. Egr-1 expression is induced in insulinoma cells and pancreatic beta-cells following stimulation with either glucose, or pregnenolone sulfate. Moreover, stithulation of G alpha q and G alpha s-coupled receptors enhances EGR-1 gene transcription. Functional studies revealed that Egr transcription factors control insulin biosynthesis via regulation of Pdx-1 expression. Glucose homeostasis and pancreatic islet size are regulated by Egr transcription factors, indicating that these proteins control central physiological parameters regulated by pancreatic beta-cells. In addition, Egr-1 is an integral part of the insulin receptor signaling cascade in insulin-responsive tissues and influences insulin resistance. (c) 2014 Elsevier Ireland Ltd. All rights reserved.