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Horm Metab Res 2001; 33(11): 639-644
DOI: 10.1055/s-2001-18691
Original Basic
© Georg Thieme Verlag Stuttgart · New York

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

Y. Zambre, C. Van Schravendijk, Z. Ling
  • Diabetes Research Center, Faculty of Medicine, Vrije Universiteit Brussel, Brussels, Belgium
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Publication Date:
04 December 2001 (online)

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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 NG-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

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Dr. Zhidong Ling

Diabetes Research Center
Vrije Universiteit Brussel

Laarbeeklaan 103
1090 Brussels
Belgium


Phone: + 32 (2) 477 45 41

Fax: + 32 (2) 477 45 45

Email: zling@mebo.vub.ac.be