Exenatide blocks JAK1-STAT1 in pancreatic beta cells

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• 作者：Francesca M. Couto ; Alex ; ra H. Minn ; Cynthia A. Pise-Masison ; Mike Radonovich ; John N. Brady ; Matthew Hanson ; Luis A. Fern ; ez ; Ping Wang ; Christina Kendziorski ; Anath Shalev
• 关键词：peanut ; Δ ; ¹² fatty acid desaturase ; prokaryotical expression ; function identification
• 刊名：Metabolism
• 出版年：2007
• 出版时间：July 2007
• 年：2007
• 卷：56
• 期：7
• 页码：915-918
• 全文大小：220 K

文摘

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.