Studies on the Conversion of Proinsulin to Insulin in the Isolated Islets of Langerhans in the Rat

Abstract

A time course study on proinsulin and insulin biosynthesis was carried out, and the results showed that proinsulin was synthesized in the microsomes and that conversion of proinsulin took place in the granule fraction (Golgi complex and granules) in isolated rat islets. When the granule fraction was incubated with exogenous ³H-labelled proinsulin for 1.5 h, no conversion of labelled proinsulin was observed. Nevertheless pulse-chase experiments showed that endogenous ³H-labelled proinsulin was converted to insulin in the granule fraction. Granular membrane and granular medium were prepared according to the method of Viverós. When endogenous ³H-labelled proinsulin was incubated with these fractions the conversion of labelled proinsulin was found only in the presence of the granular membrane fraction. The percentages of proinsulin and insulin in the total of proinsulin plus insulin changed from 80.6% and 19.4% before the incubation to 65.0% and 35.0% after the incubation. The conversion of exogenous ³H-labelled proinsulin was also found only in the presence of granular membrane. These results suggest that the granular membrane is not permeable to proinsulin and the conversion enzyme probably is bound to the membrane within the Golgi elements and/or granules.