Differential kinetics of rat insulin I and II processing in rat islets of Langerhans

Synthesis and processing of radiolabelled rat insulin I and II were studied by pulse-labelling freshly isolated rat islets with [ 3H]leucine and chasing in 2 mM glucose for up to 270 min (which minimized insulin secretion, < 1%/h). Islet samples were taken during the chase period and analyzed for their rat insulin I and II content by high-performance liquid chromatography. Prior to 60 min chase rat insulin I accounted for > 85% of the radiolabelled insulin present. With longer periods of chase, the relative percentage of rat insulin II progressively increased so that by completion of proinsulin to insulin processing the two labelled rat insulins were present in the same proportion as the relative immunoreactive content, approx. 60:40% insulin I/insulin II. Thus, although islets synthesize the two insulins in proportion to their relative immunoreactive content, rat insulin I and II are processed with different kinetics.