Increase in insulin release from rat pancreatic islets by quinolone antibiotics

Abstract

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 gtM did not. 3 At the stimulatory concentration of 10 mm glucose, all quinolones augmented insulin release in a dose-dependent manner. LFLX (100 gM) 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 gM) increased insulin release augmented by forskolin (5 ,M) or 12-0-tetradecanoyl phorbol-13-acetate (100 nM) but not by raising the K' concentration from 6 to 25 mM.5 Verapamil (50 gM) or diazoxide (50-400 gM) 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.

The insulinotropic effect of fluoroquinolones

“…Our observation is in apparent contrast to data of Saraya et al [11] who had found a stimulatory effect of 300 µM gatifloxacin or temafloxacin on mouse islets in the presence of 5.5 mM glucose. Similar to our results, Maeda et al [7] found no effect of 100 µM lomefloxacin on rat islets in the presence of a basal glucose concentration (3 mM), but a threefold increase was noted when lomefloxacin was used at the exceedingly high concentration of 1 mM. The glucose dependence of the insulinotropic effect may therefore be a concentration-dependent phenomenon.…”

“…A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 10 view of the slow kinetics of the fluoroquinolones, secretion measurements based on static incubations [7,11] may underestimate the insulinotropic efficacy.…”

“…The characterization of a direct insulinotropic effect of fluoroquinolones on isolated rat pancreatic islets led to the hypothesis that a block of B-cell K ATP channels was responsible for this effect [7]. It is generally agreed that the pharmacological closure of K ATP channels leads to a depolarization of the B-cell plasma membrane and influx of calcium via voltagedependent calcium channels, which in turn activates the exocytotic machinery [8].…”

Clinicopathological Aspect of Dysglycemia in Naive and Diabetic Rats induced by the Fluoroquinolone Antibacterial Gatifloxacin

“…Briefly, GFLX was reported to cause dysglycemia (hypoglycemia or hyperglycemia) with much higher frequencies in the retrospective human surveillance [3,15], and particularly diabetes mellitus was considered to be one of the risk factors [6]. In nonclinical investigations, many studies have reported dysglycemia as a consequence of quinolone administration in mice [8] and rats [9] as well as in in vitro studies [13,17,23]. As for GFLX, Saraya et al [17] stated that it stimulated insulin secretion and inhibited -cell ATP-sensitive K + (K ATP ) channel currents in a dose-dependent manner in mouse pancreatic islets.…”

An acute experimental study to evaluate the effect of gatifloxacin on blood sugar levels in diabetic and non-diabetic rabbits

“…It therefore supports earlier reports claiming that Gatifloxacin causes increased release of insulin leading to hypoglycemia. 9,23,24 …”