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.