Different effects of glucose and glyburide on insulin secretion in rat pancreatic islets pre-exposed to interleukin-1β. Possible involvement of K+ and Ca2+ channels

n vitro islet exposure to interleukin 1 β inhibits the beta-cell response to glucose. We have studied whether a similar inhibition also occurs in response to the sulphonylurea glyburide. Rat pancreatic islets were cultured for 24 h in the presence or absence of 50 U/ml interleukin 1 β and then stimulated with either glucose or glyburide for 1 h at 37 °C. In control islets basal insulin secretion was 117±32 pg · islet-1 · h-1 (mean ± SEM, n=7) and greatly increased in response to 16.7 mmol/l glucose (2140±293) or 10 μmol/l glyburide (1464±234). When islets were pre-exposed to interleukin 1 β, insulin release was significantly reduced in response to glucose (323±80, p<0.001) but not in response to glyburide (1316±185). Since both glucose and glyburide influence beta-cell K+ and Ca2+ efflux, to further investigate this different response in islets exposed to interleukin 1β we measured both Rb+ efflux (as index of the ATP-sensitive K+ channel activity) and Ca2+ uptake. In control islets, the increased insulin secretion in response to 16.7 mmol/l glucose or 10 μmol/l glyburide was associated with a reduction of 86Rb efflux (decrement of -50±1.2 % and -49±2.3 %, respectively, mean ± SEM, n=5). In contrast, in interleukin 1βpre-exposed islets both glucose and glyburide stimulation only slightly modified 86Rb efflux (decrement of -19±1.9% and -5.3±3.1 %, respectively, n=5, p<0.001). 45Ca2+ uptake in control islets was 2.6±0.4 pmol · islet-1 · 20 min-1 under basal conditions (at 2.8 mmol/l glucose), and increased to 16.8±3.2 and 10.7±2.1 pmol · islet-1 · 20 min-1 in islets stimulated with 16.7 mmol/l glucose or 10 μmol/l glyburide, respectively (mean ± SEM, n=6). 45Ca2+ uptake in interleukin 1 β treated islets was higher than in control islets under basal conditions (4.6±0.6 pmol · islet-1 · 20 min-1 at 2.8 mmol/l glucose, p<0.05), but was significantly reduced in response to glucose 16.7 mmol/l (7.1±1.1, p<0.01 with respect to control islets). In contrast to glucose, 10 μmol/l glyburide was able to stimulate calcium uptake in interleukin 1 β treated islets in a similar way to control islets (12.8±2.5). The present data demonstrate that rat pancreatic islets treated with interleukin 1 β for 24 h lose their responsivity to glucose, but not to glyburide. The difference between the two secretagogues is associated with the persistent ability of glyburide to influence Ca2+ uptake even in islets with impaired K+-channel function.