Interleukin-1 beta induces an early decrease in insulin release, (pro)insulin biosynthesis and insulin mRNA in mouse pancreatic islets by a mechanism dependent on gene transcription and protein synthesis.
In an attempt to further characterize the mechanisms of action of recombinant interleukin-1 beta (rIL-1 beta) on mouse pancreatic islets, islets were exposed for different periods of time (6, 12 and 24 h) to 50 U/ml rIL-1 beta. After 6 h there was already a significant decrease in glucose (16.7 mM)-induced insulin release. This was followed at 12 h by a decrease in insulin mRNA contents and (pro)insulin biosynthesis and, after 24 h, by a decrease in islet insulin contents. There was no decrease in total protein biosynthesis or DNA contents in any of the studied time points and the glucose oxidation rates were not affected by rIL-1 beta after 12 h of exposure. A similar inhibition of insulin release, (pro)insulin biosynthesis and insulin mRNA content was observed 12 h after a short (2 h) exposure of the islets to rIL-beta, suggesting that a brief exposure of mouse islets to the cytokine can modify their function for several hours. When islets were exposed for 12 h to 50 U/ml rIL-1 beta in the presence of either an inhibitor of gene transcription (actinomycin D) or an inhibitor of mRNA translation (cycloheximide) there was a complete protection against the suppressive effects of rIL-1 beta on insulin release, (pro)insulin biosynthesis and insulin mRNA contents. However, when islets were exposed for 2 h to rIL-1 beta in the presence of actinomycin D, and studied 12 h later, actinomycin counteracted the inhibitory effects of rIL-1 beta on insulin release, but not on (pro)insulin biosynthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Eizirik
D L
DL
Department of Medical Cell Biology, Uppsala University, Sweden.
D000818:Animals; D004261:DNA Replication; D003609:Dactinomycin / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009924:Organ Culture Techniques; D011384:Proinsulin / Q000096:biosynthesis; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D013268:Stimulation, Chemical; D014158:Transcription, Genetic / Q000187:drug effects
D007328:Insulin; D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D003609:Dactinomycin; D011384:Proinsulin; D005947:Glucose