Stimulation of proinsulin biosynthesis by purine-ribonucleosides and D-ribose.

Inosine and guanosine were potent stimuli of proinsulin biosynthesis ([3H]leucine incorporation) in isolated pancreatic islets of the rat. The effect was nearly abolished by formycin B, an inhibitor of purine nucleoside phosphorylase, but not by D-mannoheptulose. The corresponding bases had no effect on the rate of proinsulin biosynthesis. D-ribose enhance proinsulin biosynthesis at low concentrations )0.3-0.6mM) but concentrations above 5 mM were ineffective. The effect of all three compounds was highly specific for proinsulin biosynthesis, since incorporation of [3H]leucine into other islet proteins was not significantly stimulated. The data strongly indicate that metabolic signals regulate modulation of proinsulin biosynthesis in the beta cells.