The insulinotropic effect of fluoroquinolones is counteracted by their inhibitory effect on pancreatic beta cell energy metabolism

Abstract

Rationale: Antimicrobial fluoroquinolones both stimulate and inhibit insulin secretion leading to hypo- and hyperglycemias, respectively. The insulinotropic effect is generally explained by their ability to block KATP channels in pancreatic beta cells. However, using metabolically intact primary beta cells we have found that fluoroquinolone concentrations which were sufficient to strongly inhibit KATP channel activity in open cells were unable to significantly depolarize the beta cell plasma membrane. The rationale to explore the underlying mechanism is that some fluoroquinolones, e.g. moxifloxacin, are clearly less associated with hypoglycemias than others, e.g. gatifloxacin.