Interaction of interleukin-1 with islet beta-cells. Distinction between indirect, aspecific cytotoxicity and direct, specific functional suppression.
A 5-day culture of adult rat islets with human recombinant IL-1 beta (3 U/ml) resulted in the death of most alpha-cells and 50% of beta-cells. The IL-1--exposed islet tissue contained--in addition to poorly granulated beta-cells--patches of outgrowing monolayers and dispersed activated macrophages. In purified alpha- and beta-cell preparations, no cytodestructive effects of IL-1 (as high as 30 U/ml) were noticed, indicating that the cytokine is in itself not a beta-cell--selective killer. Pure beta-cells were, on the other hand, more sensitive (from 0.3 U/ml on) than intact islets to an IL-1--induced suppression of hormone synthesis. This inhibitory action was reversible and affected predominantly the production of insulin, leading to degranulated cells with modified shape and attachment. Further studies with IL-1 should take into account that isolated islet preparations do not allow distinction between its irreversible, indirect, and aspecific beta-cell toxicity and its reversible, direct, and specific suppression of beta-cell functions. It is not yet known whether IL-1--suppressed beta-cells exhibit an altered sensitivity to beta-cell--toxic conditions.
Ling
Z
Z
Department of Metabolism, Vrige Universiteit Brussel, Belgium.
In't Veld
P A
PA
Pipeleers
D G
DG
D000818:Animals; D002449:Cell Aggregation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D005934:Glucagon / Q000378:metabolism; D007328:Insulin / Q000096:biosynthesis / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology
D007328:Insulin; D007375:Interleukin-1; D011994:Recombinant Proteins; D005934:Glucagon