Different effects of glucose and glyburide on insulin secretion in rat pancreatic islets pre-exposed to interleukin-1 beta. Possible involvement of K+ and Ca2+ channels.
In vitro islet exposure to interleukin 1 beta 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 beta 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 1 beta, 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 1 beta 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 mumol/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 1 beta pre-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).(ABSTRACT TRUNCATED AT 250 WORDS)
Buscema
M
M
Institute of Internal Medicine, Metabolism and Endocrinology, University of Catania Medical School, Italy.
Rabuazzo
A M
AM
Vinci
C
C
Caltabiano
V
V
Vigneri
R
R
Purrello
F
F
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002132:Calcium Radioisotopes; D002478:Cells, Cultured; D005947:Glucose / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D012413:Rubidium / Q000378:metabolism*; D012414:Rubidium Radioisotopes; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D015220:Calcium Channels; D002132:Calcium Radioisotopes; D007328:Insulin; D007375:Interleukin-1; D015221:Potassium Channels; D011994:Recombinant Proteins; D012414:Rubidium Radioisotopes; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose; D012413:Rubidium; D005905:Glyburide; D002118:Calcium