Interleukin-1β Inhibits Proinsulin Conversion in Rat β-Cells Via a Nitric Oxide-Dependent Pathway

Exposure of pancreatic β-cells to interleukin-1β (IL-1β) alters their protein expression and phenotype. Previous work has shown that IL-1β inhibited proinsulin conversion in rat islets, but the mechanism of this inhibition remained unknown. To investigate this phenomenon further, we examined purified rat β-cells for IL-1β-induced inhibition of proinsulin conversion and nitric oxide (NO)-dependency of this inhibitory process. Rat β-cells were cultured for 24 h with or without IL-1β and the inducible-nitric-oxide-synthase (iNOS) inhibitor N^G-methyl-L-arginine (NMA). Exposure to IL-1β suppressed proinsulin-1 and proinsulin-2 synthesis by more than 50 %. Conversion of both proinsulin isoforms was also delayed. The suppressive effects of IL-1β on proinsulin synthesis and conversion were prevented by addition of NMA. Exposure to IL-1β also decreased the expression of the proinsulin convertase (PC) PC2. This decrease in PC2 expression was NO-dependent. In conclusion, IL-1β inhibition of proinsulin conversion in rat β-cells occurs via an NO-mediated pathway.

Key words:

Proinsulin-1 - Proinsulin-2 - Reversed-Phase High-Performance Liquid Chromatography - Convertases

References

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