Summary
In vitro exposure of rat pancreatic beta cells to interleukin-1β (IL-lβ) inhibits glucose-stimulated insulin release (2140 α 239 and 323±80 pg · islet-1 · h-1 at glucose levels of 16.7 mmol/l in control and IL-l β-exposed islets, respectively, n = 7, p < 0.001). Cholera toxin (2 ηg/ml) or pertussis toxin (0.5 ηg/ml) potentiated, as expected, glucose-induced insulin release in control islets, but, in addition, when added together with IL-l β, were able to prevent the IL-l β 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-l β alone). To investigate the mechanism by which the toxins prevent the IL-l β 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-l β-exposed islets, respectively (n = 6, p = 0.05). In islets exposed to IL-l β 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-l β-treated islets (p < 0.05). The addition of cholera or pertussis toxins simultaneously to IL-l β prevented the inhibition of glucose oxidation at 16.7 mmol/l glucose (32.9±3.8 and 31.7±3.3 pmol · islet-1 · 120 min-1 in the presence of cholera or pertussis toxins, respectively). Glucose-stimulated 45Ca2+ uptake was also significantly inhibited in IL-l β-treated islets when compared to control islets (7.1±0.9 and 16.8±3.2 pmol · islet-1 · 20 min-1, respectively, p < 0.05). This inhibition was prevented by the presence of cholera or pertussis toxins (14.0±3.8 and 11.2±2.7 pmol · islet-1 · 20 min-1, respectively). In conclusion, our data show that cholera and, to a lesser extent, pertussis toxins are able to partially prevent the IL-lβ-induced increase in nitrite levels and block the inhibitory effects of IL-lβ on different steps leading to glucose-induced insulin secretion. These findings support the possibility that in pancreatic beta cells, G-proteins may be involved or interfere with the cytokine signal transduction.
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Abbreviations
- IL-lβ:
-
Interleukin 1β
- CT:
-
cholera toxin
- PT:
-
pertussis toxin
- NO:
-
nitric oxide
- FCS:
-
fetal calf serum
- KRHB:
-
Krebs-Ringer Hepes buffer
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Rabuazzo, A.M., Buscema, M., Caltabiano, V. et al. Interleukin-1β inhibition of insulin release in rat pancreatic islets: Possible involvement of G-proteins in the signal transduction pathway. Diabetologia 38, 779–784 (1995). https://doi.org/10.1007/s001250050352
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DOI: https://doi.org/10.1007/s001250050352