REPAGLINIDE PRESERVES NUTRIENT-STIMULATED BIOSYNTHETIC ACTIVITY IN RAT PANCREATIC-ISLETS

The meglitinide analogue repaglinide is a novel non-sulphonylurea insu linotropic agent which, like hypoglycaemic sulphonylureas, causes the closing of ATP-sensitive K+ channels in islet cells. We have now explo red the effect of repaglinide upon proinsulin biosynthesis in rat panc reatic islets. Groups of eight islets each were incubated for 90 min i n the presence of L-[4-H-3]phenylalanine (4 mu m) and glucose (2.8 or 16.7 mM), in the absence or presence of repaglinide (10 mu M). A rise in glucose concentration caused a four-fold increase of the incorporat ion of L-[4-H-3]phenylalanine into TCA-precipitable material. Repaglin ide failed to adversely affect protein biosynthesis, whether at low or high glucose concentrations. Further characterization of the biosynth etic response was achieved by separation of the tritiated peptides by gel filtration. In the absence of repaglinide, the (pro)insulin/total ratio of tritiated peptides averaged 33.3+/-10.2 and 58.7+/-1.7% (n=6 in both cases) at 2.8 and 16.7 mM D-glucose, respectively. Repaglinide again failed to significantly affect such ratios. In conclusion, repa glinide may offer the advantage over hypoglycaemic sulphonylureas of p reserving nutrient-stimulated biosynthetic activity in pancreatic isle t cells. (C) 1996 The Italian Pharmacological Society