SIGNALS RELATED TO GLUCOSE-METABOLISM REGULATE ISLET AMYLOID POLYPEPTIDE (IAPP) GENE-EXPRESSION IN HUMAN PANCREATIC-ISLETS

Intracellular pathways involved in glucose stimulation of IAPP gene ex pression were studied in human pancreatic islets. Glucose (16.7 mM), b ut not mannose, caused a 2.3-fold increase in IAPP mRNA levels; this e ffect was inhibited by actinomycin D. In the presence of the non-metab olizable 6-deoxyglucose (16.7 mM) IAPP mRNA levels were markedly deple ted. Both mannoheptulose and verapamil blocked glucose-induced stimula tion of the IAPP gene. The magnitude of the insulin gene response to g lucose 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 gluco se media, respectively; however, it did nor change insulin mRNA. It ha d no effect on rat IAPP or insulin mRNAs, either. We conclude that IAP P gene expression is regulated by signals derived from glucose metabol ism and that intracellular calcium may be involved in this response. I APP and insulin genes are nor co-regulated in cultured human pancreati c islets. (C) 1997 Elsevier Science B.V.