Signals related to glucose metabolism regulate islet amyloid polypeptide (IAPP) gene expression in human pancreatic islets

Abstract

Intracellular pathways involved in glucose stimulation of IAPP gene expression were studied in human pancreatic islets. Glucose (16.7 mM), but not mannose, caused a 2.3-fold increase in IAPP mRNA levels; this effect was inhibited by actinomycin D. In the presence of the non-metabolizable 6-deoxyglucose (16.7 mM) IAPP mRNA levels were markedly depleted. Both mannoheptulose and verapamil blocked glucose-induced stimulation of the IAPP gene. The magnitude of the insulin gene response to glucose was smaller (1.3-fold); none of the above-mentioned agents had significant effects on insulin mRNA content. Tunicamycin elicited a 2.4- and 2.7-fold increase in IAPP mRNA levels in the low and high glucose media, respectively; however, it did not change insulin mRNA. It had no effect on rat IAPP or insulin mRNAs, either. We conclude that IAPP gene expression is regulated by signals derived from glucose metabolism and that intracellular calcium may be involved in this response. IAPP and insulin genes are not co-regulated in cultured human pancreatic islets.