Exenatide blocks JAK1-STAT1 in pancreatic beta cells

Academic Article

Abstract

  • Exenatide (Ex-4) is an antidiabetic drug that acts through the glucagon-like peptide 1 receptor and has recently been approved for the treatment of type 2 diabetes mellitus. Ex-4 also has been shown to affect beta cell gene expression and increase beta cell mass in rodent models of type 1 diabetes mellitus, but the mechanisms are not fully understood. We therefore analyzed the pathways affected by Ex-4 in human islets by using oligonucleotide microarrays and the PathwayStudio software (Ariadne Genomics, Rockville, MD). We identified the JAK1-STAT1 pathway as a novel target of Ex-4 and confirmed the Ex-4-mediated down-regulation of JAK1 and STAT1 by quantitative reverse transcription-polymerase chain reaction in human islets and INS-1 cells. JAK1-STAT1 is the major signaling pathway mediating the interferon γ effects on beta cell apoptosis in type 1 diabetes mellitus. Thus, these findings suggest that Ex-4 treatment may also be beneficial in type 1 diabetes mellitus, where it may help protect beta cells from cytokine-induced cell death by inhibiting JAK1-STAT1. © 2007 Elsevier Inc. All rights reserved.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Couto FM; Minn AH; Pise-Masison CA; Radonovich M; Brady JN; Hanson M; Fernandez LA; Wang P; Kendziorski C; Shalev A
  • Start Page

  • 915
  • End Page

  • 918
  • Volume

  • 56
  • Issue

  • 7