DIFFERENT EFFECTS OF GLUCOSE AND GLYBURIDE ON INSULIN-SECRETION IN RAT PANCREATIC-ISLETS PREEXPOSED TO INTERLEUKIN-1-BETA - POSSIBLE INVOLVEMENT OF K+ AND CA2+ CHANNELS

In vitro islet exposure to interleukin 1beta inhibits the beta-cell re sponse to glucose. We have studied whether a similar inhibition also o ccurs in response to the sulphonylurea glyburide. Rat pancreatic islet s were cultured for 24 h in the presence or absence of 50 U/ml interle ukin 1beta and then stimulated with either glucose or glyburide for 1 h at 37-degrees-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 mumol/l glyburide (1464 +/- 234). When islets were pre-exposed to interleukin 1beta, in sulin release was significantly reduced in response to glucose (323 +/ - 80, p < 0.001) but not in response to glyburide (1316 +/- 185). Sinc e both glucose and glyburide influence beta-cell K+ and Ca2+ efflux, t o further investigate this different response in islets exposed to int erleukin 1beta we measured both Rb- efflux (as index of the ATP-sensit ive K+ channel activity) and Ca2+ uptake. In control islets, the incre ased insulin secretion in response to 16.7 mmol/l glucose or 10 mumol/ l glyburide was associated with a reduction of Rb-86 efflux (decrement of -50 +/- 1.2 % and -49 +/- 2.3 %, respectively, mean +/- SEM, n = 5 ). In contrast, in interleukin 1beta pre-exposed islets both glucose a nd glyburide stimulation only slightly modified Rb-86 efflux (decremen t of -19 +/- 1.9 % and -5.3 +/- 3.1 %, respectively, n = 5, p < 0.001 ). Ca-45(2+) uptake in control islets was 2.6 +/- 0.4 mumol . islet-1 . 20 min-1 under basal conditions (at 2.8 mmol/l glucose), and increas ed to 16.8 +/- 3.2 and 10.7 +/- 2.1 pmol . islet-1. 20 min-1 in islets stimulated with 16.7 mmol/I glucose or 10 mumol/l glyburide, respecti vely (mean +/- SEM, n = 6). Ca-45(2+) uptake in interleukin 1beta trea ted is lets 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 glu cose, 10 mumol/l glyburide was able to stimulate calcium uptake in int erleukin 1beta treated islets in a similar way to control islets (12.8 +/- 2.5). The present data demonstrate that rat pancreatic islets tre ated with interleukin 1beta for 24 h lose their responsivity to glucos e, but not to glyburide. The difference between the two secretagogues is associated with the persistent ability of glyburide to influence Ca 2+ uptake even in islets with impaired K+-channel function.