The insulin-producing pancreatic islet β-cell, characterized by low proliferative potential, is normally not responsive to the polypeptide epidermal growth factor (EGF) or its homolog transforming growth factor α (TGF-α). Since EGF receptors in other tissues can be up-regulated by other growth factors and by cytokines, we have in this paper investigated whether such a β-cell responsiveness to TGF-α, or EGF, can be conferred by co-culture with interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) or transforming growth factor β (TGF-β) in various combinations. To this end, fetal rat pancreatic islets enriched in β-cells were isolated and cultured for 3 days with or without 200 pM or 20 nM TGF-α. It was found that neither of these TGF-α concentrations affected β-cell mitogenesis, insulin content or insulin secretion. However, IFN-γ (1000 U/ml) evoked a modest stimulation of β-cell replication, while suppressing insulin secretion and leaving the islet insulin content unaltered. TNF-α (1000 U/ml), on the other hand, affected none of these parameters either alone or in any combination with TGF-α or IFN-γ. However, when TNF-α or IFN-γ, either alone or in combination, were combined with the cytokine interleukin-1β, this resulted in islet disintegration, whereas the latter cytokine alone did not exert any gross necrotic changes evident by light microscopy. TGF-β (500 pM) stimulated insulin secretion but did not influence islet insulin content or β-cell mitogenesis either alone or in combination with TGF-α (200 pM or 20 nM). In no instance could any mitogenic or secretory response to low or high concentrations of TGF-α be conferred by IFN-γ, TNF-α or TGF-β whether used alone or in combinations. Hence, responsiveness to TGF-α or EGF in the β-cell obviously cannot be achieved by any of these peptides.
Effects of transforming growth factor β, tumor necrosis factor α and interferon γ on pancreatic islet β-cell responsiveness to transforming growth factor α
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Åke Sjöholm; Effects of transforming growth factor β, tumor necrosis factor α and interferon γ on pancreatic islet β-cell responsiveness to transforming growth factor α. Biosci Rep 1 October 1996; 16 (5): 415–423. doi: https://doi.org/10.1007/BF01207266
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