Effects of islet amyloid polypeptide (IAPP) on insulin biosynthesis or secretion in rat islets and mouse βTC3 cells. Biosynthesis of IAPP in mouse βTC3 cells

Abstract

Effects of rat islet amyloid polypeptide (IAPP) on insulin biosynthesis and secretion were examined in isolated rat islets and mouse βTC3 cells. Culture of islets or mouse βTC3 cells for 24 h in the presence of 10 −6 M IAPP and 5.5 mM glucose had no effect on insulin mRNA levels. The rates of proinsulin biosynthesis were not altered in islets incubated in 10 −4–10 −9 M IAPP. In βTC3 cells, proinsulin biosynthesis was stimulated by glucose, though no effects of IAPP were shown. Addition of 10 −5 M IAPP to islets incubated in 11 mM glucose decreased the fractional insulin secretion rates; however, the secretion of insulin from βTC3 cells was not affected by 10 −5 M IAPP. On the other hand, mouse βTC3 cells expressed the elevated level of IAPP mRNA. Metabolic labeling of βTC3 cells revealed the synthesis of both proIAPP and mature IAPP. In pulse chase experiments, proIAPP was processed to IAPP in a manner similar to proinsulin. These data indicate that IAPP is a possible polypeptide hormone synthesized in pancreatic β cells though it is unlikely that IAPP is a physiologically relevant modulator of insulin biosynthesis or secretion.