title: Effect of interleukin-1 on the biosynthesis of proinsulin and insulin in isolated rat pancreatic islets.
abstract: Insulin dependent diabetes mellitus (IDDM) is often preceded or associated with lymphocytic infiltration in the islets of Langerhans (insulitis). We recently demonstrated that interleukin-1 (IL-1) produced by activated macrophages exerts a bimodal effect on insulin release and biosynthesis in isolated rat islets. In the present study we have further analysed the effect of recombinant human interleukin-1 beta (rIL-1) on the biosynthesis and conversion of proinsulin 1 and 2 in rat islets. By RP-HPLC-analysis of islets labelled with [3H]leucine we found that exposure to 6 ng/ml of IL-1 for 24 h reduced the insulin biosynthesis to 6.1 +/- 2.7% (n = 4). During the 3 h labelling period the labelled proinsulin content compared to insulin was increased from 9.0 +/- 1.3% (control) to 26.6 +/- 6.4% in the IL-1 exposed islets, and the ratio between labelled insulin 1 to 2 was increased from 2.0 +/- 0.1 to 3.4 +/- 0.4, respectively. Pulse-chase experiments with [3H]leucine and [35S]methionine indicated a more marked reduction in the conversion rate of proinsulin-2 compared to that of proinsulin-1. In conclusion these experiments demonstrate that IL-1 inhibits insulin biosynthesis by preferential attenuation of the rate of conversion of proinsulin 2.
authors.affiliation: Hagedorn Research Laboratory, Gentofte, Denmark.
authors.forename: B S
authors.initials: BS
authors.lastname: Hansen
authors.forename: J H
authors.initials: JH
authors.lastname: Nielsen
authors.forename: S
authors.initials: S
authors.lastname: Linde
authors.forename: G A
authors.initials: GA
authors.lastname: Spinas
authors.forename: B S
authors.initials: BS
authors.lastname: Welinder
authors.forename: T
authors.initials: T
authors.lastname: Mandrup-Poulsen
authors.forename: J
authors.initials: J
authors.lastname: Nerup
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D007328:Insulin / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D011384:Proinsulin / Q000096:biosynthesis*; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology*
chemical_list: D007328:Insulin; D007375:Interleukin-1; D011994:Recombinant Proteins; D011384:Proinsulin