Interleukin-1 beta inhibition of insulin release in rat pancreatic islets: possible involvement of G-proteins in the signal transduction pathway.
In vitro exposure of rat pancreatic beta cells to interleukin-1 beta (IL-1 beta) inhibits glucose-stimulated insulin release (2140 +/- 239 and 323 +/- 80 pg.islet-1.h-1 at glucose levels of 16.7 mmol/l in control and IL-1 beta-exposed islets, respectively, n = 7, p < 0.001). Cholera toxin (2 micrograms/ml) or pertussis toxin (0.5 microgram/ml) potentiated, as expected, glucose-induced insulin release in control islets, but, in addition, when added together with IL-1 beta, were able to prevent the IL-1 beta mediated inhibition of glucose-stimulated insulin secretion (2087 +/- 301 and 1662 +/- 173 pg.islet-1.h-1, respectively, p < 0.05 vs islets exposed to IL-1 beta alone). To investigate the mechanism by which the toxins prevent the IL-1 beta effect, we then measured nitrite levels, glucose oxidation and Ca2+ uptake. Nitrite levels in the culture medium were 4.2 +/- 1.4 and 24.0 +/- 5 pmol.islet-1.24 h-1 in control islets and in IL-1 beta-exposed islets, respectively (n = 6, p = 0.05). In islets exposed to IL-1 beta and cholera or pertussis toxins, nitrite levels were 9.1 +/- 3 and 12.4 +/- 6 pmol.islet-1.24 h-1, respectively (n = 6, NS vs control islets). Glucose oxidation at 16.7 mmol/l glucose was 31.1 +/- 2.9 pmol.islet-1.120 min-1 in control islets and 16.8 +/- 2.7 pmol.islet-1.120 min-1 in IL-1 beta-treated islets (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Rabuazzo
A M
AM
Institute of Internal Medicine, Metabolism and Endocrinology, University of Catania Medical School, Italy.
Buscema
M
M
Caltabiano
V
V
Anello
M
M
Degano
C
C
Patanè
G
G
Vigneri
R
R
Purrello
F
F
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D004347:Drug Interactions; D019204:GTP-Binding Proteins / Q000502:physiology*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009573:Nitrites / Q000032:analysis / Q000378:metabolism; D037342:Pertussis Toxin; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007328:Insulin; D007375:Interleukin-1; D009573:Nitrites; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; D002772:Cholera Toxin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D005947:Glucose; D002118:Calcium