Figure 2.

Regulatory mechanisms driving IAPP transcription in normal and stressed pancreatic β-cells. (1) High glucose induces expression of the major glucose regulated gene TXNIP, which, in turn, upregulates IAPP transcription by increasing the expression and promoter binding of IAPP specific transcription factor FoxA2 in the β-cell. (2) Similarly, ER stress upregulates IAPP transcription in β-cells by increasing IAPP promoter’s occupancy for transcription factor FoxA2, for which the binding of could be TXNIP-dependent or independent. (3) Severe inhibition of proteasome function and associated protein stress downregulate IAPP transcription by attenuating FoxA2 binding at the IAPP promoter in the β-cell. Green arrows depict positive regulatory pathways, and red arrow depicts an inhibitory pathway. Different signaling branches are numbered. Dashed arrows depict hypothetical signaling branches.