Effects of fluoroquinolones on insulin secretion and beta-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 Kir6.2 Delta C26 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.
Saraya
Atsunori
A
Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan.
Yokokura
Masaaki
M
Gonoi
Tohru
T
Seino
Susumu
S
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D002478:Cells, Cultured; D024841:Fluoroquinolones / Q000009:adverse effects*; D000077734:Gatifloxacin; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D064704:Levofloxacin; D051379:Mice; D015242:Ofloxacin / Q000009:adverse effects; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology*; D015363:Quinolones / Q000009:adverse effects
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D007328:Insulin; D015221:Potassium Channels; D015363:Quinolones; C054745:temafloxacin; D064704:Levofloxacin; D000255:Adenosine Triphosphate; D015242:Ofloxacin; D000077734:Gatifloxacin