Effect of interleukin-1 on the biosynthesis of proinsulin and insulin in isolated rat pancreatic islets
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Effect of interleukin-1 on the biosynthesis of proinsulin and insulin in isolated rat pancreatic islets. / Hansen, Birgit Sehested; Linde, S; Spinas, G A; Welinder, B S; Mandrup-Poulsen, T; Nerup, J; Nielsen, Jens Høiriis.
I: Biomedica Biochimica Acta, Bind 47, Nr. 4-5, 1988, s. 305-9.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Effect of interleukin-1 on the biosynthesis of proinsulin and insulin in isolated rat pancreatic islets
AU - Hansen, Birgit Sehested
AU - Linde, S
AU - Spinas, G A
AU - Welinder, B S
AU - Mandrup-Poulsen, T
AU - Nerup, J
AU - Nielsen, Jens Høiriis
PY - 1988
Y1 - 1988
N2 - 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.
AB - 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.
KW - Animals
KW - Cells, Cultured
KW - Humans
KW - Insulin
KW - Interleukin-1
KW - Islets of Langerhans
KW - Kinetics
KW - Proinsulin
KW - Rats
KW - Recombinant Proteins
M3 - Journal article
C2 - 3071362
VL - 47
SP - 305
EP - 309
JO - Biomedica Biochimica Acta
JF - Biomedica Biochimica Acta
SN - 0232-766X
IS - 4-5
ER -
ID: 47974767