Chronic exposure of cultured rat pancreatic islets to elevated concentrations of islet amyloid polypeptide (IAPP)...

The biological action of islet amyloid polypeptide (IAPP) remains to be established, although a role for IAPP in causing beta-cell failure in diabetes has been proposed. Acute in vitro experiments with IAPP have given controversial results as to beta-cell insulin secretion. We have studied the effect of a long-term exposure of pancreatic islets to elevated IAPP concentrations. Thus, rat pancreatic islets were cultured for 4 days in medium supplemented with 0, 0.1, 1, 10, 100 or 1000 nM of synthetic amidated rat IAPP. Islets exposed to the two highest IAPP concentrations contained about 20% less DNA, whereas the rate of DNA synthesis was unchanged. Culture with 1000 nM IAPP, but not the lower concentrations of the peptide, slightly decreased the glucose oxidation rate. There was a correlation between increasing IAPP concentrations and and a decline in the medium insulin accumulation. The preceding IAPP exposure did, however, neither significantly affect basal and glucose-stimulated insulin secretion nor (pro)insulin and total protein biosynthesis rates, when tested after the culture. The finding of a decreased islet cell DNA content after culture with elevated IAPP concentrations suggests a toxic action to islet cells, whereas a putative inhibition of the islet insulin production appears to be transient.