Lack of Islet Amyloid Polypeptide Regulation of Insulin Biosynthesis or Secretion in Normal Rat Islets

We examined the effects of rat islet amyloid polypeptide (IAPP) on insulin biosynthesis and secretion by isolated rat islets of Langerhans. Culture of islets for 24 h in the presence of 10⁻⁶ M IAPP and 5.5 mM glucose had no effect on insulin mRNA levels. Similarly, the rates of proinsulin biosynthesis were not altered in islets incubated in 10⁻⁴–10⁻⁹ M IAPP and 5.5 mM glucose, nor was the rate of conversion of proinsulin to insulin changed at 10⁻⁶ M IAPP. Addition of 10⁻⁵ M IAPP to islets incubated in 11 mM glucose decreased the fractional insulin secretion rate; however, the secretion of newly synthesized proinsulin and insulin was not affected. These data indicate that it is unlikely that IAPP is a physiologically relevant modulator of insulin biosynthesis or secretion.