Increase in insulin release from rat pancreatic islets by quinolone antibiotics.
1. The present study was undertaken to elucidate the mechanism(s) of hypoglycaemia caused by quinolone antibiotics. We investigated the effects of various quinolone antibiotics on insulin release in rat pancreatic islets. 2. At a non-stimulatory concentration of 3 mM glucose, lomefloxacin (LFLX) or sparfloxacin at 1 mM and pipemidic acid (0.1-1 mM) induced slight insulin release but tosufloxacin or enoxacin up to 100 microM did not. 3. At the stimulatory concentration of 10 mM glucose, all quinolones augmented insulin release in a dose-dependent manner. LFLX (100 microM) 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 microM) increased insulin release augmented by forskolin (5 microM) or 12-O-tetradecanoyl phorbol-13-acetate (100 nM) but not by raising the K+ concentration from 6 to 25 mM. 5. Verapamil (50 microM) or diazoxide (50-400 microM) antagonized the insulinotropic effect of LFLX. 6. These data suggest that quinolone antibiotics may cause hypoglycaemia by increasing insulin release via blockade of ATP-sensitive K+ channels.
Maeda
N
N
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Tamagawa
T
T
Niki
I
I
Miura
H
H
Ozawa
K
K
Watanabe
G
G
Nonogaki
K
K
Uemura
K
K
Iguchi
A
A
D042462:4-Quinolones; D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D003981:Diazoxide / Q000494:pharmacology; D004232:Diuretics; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology; D013268:Stimulation, Chemical; D014700:Verapamil / Q000494:pharmacology
D042462:4-Quinolones; D000890:Anti-Infective Agents; D002121:Calcium Channel Blockers; D004232:Diuretics; D007328:Insulin; D015221:Potassium Channels; D049993:Sodium Chloride Symporter Inhibitors; D000255:Adenosine Triphosphate; D014700:Verapamil; D000242:Cyclic AMP; D005947:Glucose; D003981:Diazoxide