Background: Islet amyloid polypeptide (IAPP) plays an important role in beta-cell biology, but its regulation is not fully understood. Results: Thioredoxin-interacting protein (TXNIP) induces IAPP by inhibiting miR-124a and promoting FoxA2-mediated transcription. Conclusion: The critical beta-cell signaling pathways of TXNIP and IAPP are linked. Significance: Identification of this novel TXNIP/miR-124a/FoxA2/IAPP signaling pathway provides new insight into an important aspect of transcriptional regulation and beta-cell biology. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.