Glucose regulated insulin biosynthesis in isolated rat pancreatic islets is accompanied by changes in proinsulin mRNA

Isolated rat pancreatic islets were incubated in high (28 mM) or low (2.8 mM) glucose for 0, 1 or 4 hr and insulin biosynthesis and messenger RNA quantified. During the 4 hr course of the experiments the fraction of protein synthesised specifically into proinsulin increased in the presence of high vs low glucose (14.3 +/- 3.7 vs 0.8 +/- 0.5%, p less than 0.01). The relative amount of proinsulin mRNA was found to be about 5-fold higher in islets incubated in high glucose at 4 hr as determined by RNA blot hybridization. Total translatable islet mRNA was unaffected by glucose in the medium. These data extend observations of changes in proinsulin mRNA in rats in vivo during fasting and glucose injection, and suggest a direct effect of glucose on islets. These data further demonstrate that glucose modulates selectively the level of proinsulin mRNA during incubation of isolated pancreatic islets and that changes in the level of proinsulin mRNA play an important role in regulation of insulin biosynthesis.