ISSN:
1432-0428
Keywords:
Key words Interleukin-1β
;
pertussis toxin
;
cholera toxin
;
pancreatic islets
;
insulin secretion
;
G-proteins
;
nitric oxide.
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary In vitro exposure of rat pancreatic beta cells to interleukin-1β (IL-1β) 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-1β-exposed islets, respectively, n = 7, p 〈 0.001). Cholera toxin (2 μg/ml) or pertussis toxin (0.5 μg/ml) potentiated, as expected, glucose-induced insulin release in control islets, but, in addition, when added together with IL-1β, were able to prevent the IL-1β 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-1β alone). To investigate the mechanism by which the toxins prevent the IL-1β 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-1β-exposed islets, respectively (n = 6, p = 0.05). In islets exposed to IL-1β 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-1β-treated islets (p 〈 0.05). The addition of cholera or pertussis toxins simultaneously to IL-1β 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 + up-take was also significantly inhibited in IL-1β-treat-ed 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-1β-induced increase in nitrite levels and block the inhibitory effects of IL-1β 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. [Diabetologia (1995) 38: 779–784]
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s001250050352
