Interleukin-1beta induces ornithine decarboxylase activity in insulin-producing cells.
Cytokines might play a role in the development of insulin-dependent diabetes. Interleukin 1beta (IL-1beta) has been shown to alter the functional state of insulin-producing beta cells. This effect appears mediated through induction of certain proteins and suppression of others. The present study demonstrates that the ornithine decarboxylase (ODC) activity of rat beta cells and insulin-producing rat insulinoma (RIN) cells increases more than three-fold within 2 h of IL-1beta exposure. Both basal and IL-1 beta induced ODC activities completely disappear following a 2 h block of protein translation. In Western blot analysis, a 51-kDa protein varies in parallel with the ODC-activity. Exposure to IL-1beta increases the 51-kDa band through an effect at the transcriptional level. The higher cellular ODC activity in IL-1beta treated RIN cells is associated with an increased cellular content of its enzymatic product putrescine, but not of putrescine-derived products such as polyamines and GABA. The 30-fold lower ODC activity in rat beta cells forms a technical obstacle to studies on the regulation and functional significance of this enzyme in normal cells. The present findings list ODC-activity as an early response to the effect of interleukin 1beta on the transcriptional activity in insulin-producing cells. Further work is needed to identify whether ODC activation contributes to the previously described functional changes in pancreatic beta cells.
Smismans
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A
Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, B-1090, Belgium.
Eizirik
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Pipeleers
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DG
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004790:Enzyme Induction; D007328:Insulin / Q000096:biosynthesis; D007340:Insulinoma / Q000201:enzymology* / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism*; D007515:Islets of Langerhans / Q000201:enzymology*; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured
D007328:Insulin; D007375:Interleukin-1; D011073:Polyamines; D009955:Ornithine Decarboxylase