IAPP/amylin gene transcriptional control region: evidence for negative regulation

Abstract
Aberrant expression of the islet amyloid polypeptide (IAPP) gene might be involved in the pathogenesis of nun‐insulin‐dependent diabetes mellitus (NIDDM). Here, we report that IAPP promoter‐luciferase constructs revealed tissue‐specific activity. This activity was not mediated by cAMP. Sequential 5' deletions of the IAPP promoter caused a progressive derepression of the IAPP gene promoter in IAPP‐producing cells. Comparison of the nucleotide sequence of the IAPP promoter with that of the insulin promoter (both active in pancreatic β‐cells) reveals two sequence elements of putative importance: an insulin enhancer‐like sequence and an element which corresponds to a protected domain in rat insulin I gene promoter footprint experiments.