Summary
Interleukin 1β, potentiated by tumour necrosis factor α, is cytotoxic to pancreatic Beta cells in vitro. We have hypothesized that interleukin 1β induces oxygen free radicals in Beta cells. Since cytotoxicity induced by free radicals and by heat may activate the same cellular repair mechanism (the heat shock response), the aim of this study was to investigate the pattern of protein synthesis in isolated islets after exposure to interleukin 1β (150 pg/ml, 24 h), tumour necrosis factor α (50 ng/ml, 24 h), heat shock (43°C, 30 min) and H2O2 (0.1 mmol/l, 20 min). By polyacrylamide gel electrophoresis, autoradiography, Western-blot analysis and partial peptide mapping of 35S-methionine labelled islets, interleukin 1β was found to induce a 73 kilodalton protein belonging to the heat shock protein family heat shock protein 70, a heat shock protein 90, and haem oxygenase. A minor induction of heat shock protein 73 and haem oxygenase was seen after H2O2. Interleukin 1β did not induce heat shock proteins in rat thyroid cells, rat mesangial cells or in human monocytes. Tumour necrosis factor α did not induce selective protein synthesis. Pre-exposure of islets to heat, tumour necrosis factor α, or H2O2 did not prevent the impairment of glucose-stimulated insulin release seen after 24 h of interleukin 1β exposure. The data are compatible with free radical induction by interleukin 1β. However, the heat shock response is not specific for oxidative injury, and previous studies have shown discrepant effects as to a protective effect of free radical scavengers against interleukin 1β-mediated beta-cytotoxicity. Thus, a role for free radicals in this context is not definitely proven.
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Helqvist, S., Polla, B.S., Johannesen, J. et al. Heat shock protein induction in rat pancreatic islets by recombinant human interleukin 1β. Diabetologia 34, 150–156 (1991). https://doi.org/10.1007/BF00418268
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DOI: https://doi.org/10.1007/BF00418268