INCREASE IN INSULIN RELEASE FROM RAT PANCREATIC-ISLETS BY QUINOLONE ANTIBIOTICS

1 The present study was undertaken to elucidate the mechanism(s) of hy poglycaemia caused by quinolone antibiotics. We investigated the effec ts of various quinolone antibiotics on insulin release in rat pancreat ic islets. 2 At a non-stimulatory concentration of 3 mM glucose, lomef loxacin (LFLX) or sparfloxacin at 1 mM and pipemidic acid (0.1-1 mM) i nduced slight insulin release but tosufloxacin or enoxacin up to 100 m u M did not. 3 At the stimulatory concentration of 10 mM glucose, all quinolones augmented insulin release in a dose-dependent manner. LFLX (100 mu M) shifted the dose-response curve of glucose-induced insulin release to the left without altering the maximal response. 4 At 10 mM glucose, LFLX (100 mu M) increased insulin release augmented by forsko lin (5 mu M) or 12-O-tetradecanoyl phorbol-13-acetate (100 nM) but not by raising the K+ concentration from 6 to 25 mM. 5 Verapamil (50 mu M ) or diazoxide (50-400 mu M) antagonized the insulinotropic effect of LFLX. 6 These data suggest that quinolone antibiotics may cause hypogl ycaemia by increasing insulin release via blockade of ATP-sensitive K channels.