Effects of fluoroquinolones on insulin secretion and β-cell ATP-sensitive K+ channels

Although fluoroquinolones are used widely in the treatment of various infectious diseases, some of the drugs are known to cause hypoglycemia as a side-effect. We have investigated the effects of three fluoroquinolone derivatives, levofloxacin, gatifloxacin, and temafloxacin, on insulin secretion and pancreatic beta-cell ATP-sensitive K+ channel (K-ATP channel) activity. While levofloxacin had only a small effect on insulin secretion and K-ATP currents, gatifloxacin and temafloxacin stimulated insulin secretion and inhibited K-ATP channel currents in a dose-dependent manner. We also determined the site of action of gatifloxacin and temafloxacin on the K-ATP channel. In a reconstituted system, gatifloxacin and temafloxacin inhibited Kir6.2DeltaC26 channels, which function in the absence of the SUR subunit, indicating direct action of the drugs on the Kir6.2 subunits. These results suggest that stimulation of insulin secretion by inhibition of pancreatic beta-cell K-ATP channels underlies the hypoglycemia caused by certain fluoroquinolones. (C) 2004 Elsevier B.V. All rights reserved.