Effects of islet amyloid polypeptide (IAPP) on insulin biosynthesis or secretion in rat islets and mouse beta TC3 cells. Biosynthesis of IAPP in mouse beta TC3 cells.

Effects of rat islet amyloid polypeptide (IAPP) on insulin biosynthesis and secretion were examined in isolated rat islets and mouse beta TC3 cells. Culture of islets or mouse beta TC3 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 beta TC3 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 beta TC3 cells was not affected by 10(-5) M IAPP. On the other hand, mouse beta TC3 cells expressed the elevated level of IAPP mRNA. Metabolic labeling of beta TC3 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 beta cells though it is unlikely that IAPP is a physiologically relevant modulator of insulin biosynthesis or secretion.