Decreased cell replication and polyamine content in insulin-producing cells after exposure to human interleukin 1 beta.
Interleukin 1 (IL-1) has been suggested to cause the islet B cell destruction occurring during the development of insulin-dependent diabetes mellitus. One mechanism by which B cell loss can be compensated for is via de novo formation of new cells through replication. In the present study the replicatory activity of cells in isolated rat pancreatic islets and in the insulin-producing cell line RINm5F has been assessed by [3H]thymidine incorporation methods after exposure to 1-25 U/ml of human recombinant IL-1 beta (rIL-1 beta). In the rat islets [3H]thymidine incorporation was decreased by 20% 5 h after exposure to 25 U/ml rIL-1 beta. A similar inhibition was also observed in islets exposed to 2.5 and 12.5 U/ml rIL-1 beta. In the RINm5F cells there was a dose-dependent inhibition of the cell replication to approximately 50% of the controls in cells exposed to 25 U/ml rIL-1 beta for 48 h. This was also accompanied by an increased cell death, as measured by trypan blue inclusion (controls 13% and rIL-1 beta treated cells 25%). The insulin content of the RINm5F cells was reduced by about 40% after a 48-h exposure to 25 U/ml rIL-1 beta. When the exposure of the RINm5F cells to rIL-1 beta was decreased to 24 h there was no increased cell death, but a reduced replicatory activity was still observed. rIL-1 beta decreased the cellular content of the polyamines spermidine and spermine.(ABSTRACT TRUNCATED AT 250 WORDS)
Sandler
S
S
Department of Medical Cell Biology, Uppsala University, Sweden.
Bendtzen
K
K
Eizirik
D L
DL
Sjöholm
A
A
Welsh
N
N
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D046508:Culture Techniques; D007328:Insulin / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011073:Polyamines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins; D013997:Time Factors; D014407:Tumor Cells, Cultured
D007328:Insulin; D007375:Interleukin-1; D011073:Polyamines; D011994:Recombinant Proteins