Short- and long-term effects of β-cellulin and transforming growth factor-α on β-cell function in cultured fetal rat pancreatic islets
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The polypeptide β-cellulin, identified in conditioned media from insulinoma cell cultures and produced by pancreatic islet cells, was recently identified as a possible autocrine growth factor for the pancreatic islet β-cell. In this study, we investigated the short- and long-term actions of β-cellulin, and the structurally related transforming growth factor-α (TGF-α), on β-cell function in fetal rat pancreatic islets in vitro. We found that neither β-cellulin nor TGF-α (10 nMeach), in contrast to glucose (20 mM), acutely influenced β-cell levels of cytosolic-free Ca2+. Additionally, whereas glucose markedly increased short-term (60-min) insulin release, neither β-cellulin nor TGF-α (10nM each) influenced the rate of hormone secretion at basal (3 mM) or stimulatory (20 mM) concentrations of glucose. Likewise, long-term (24-h) exposure of islets to a high glucose concentration significantly augmented the secretion of insulin. This effect was slightly potentiated by TGF-α (10 nM), but not β-celluin (10 nM), at high (but not low) glucose concentrations. Conversely, the islet insulin content was not significantly affected by β-cellulin or TGF-α at any glucose concentration tested. We conclude that, although β-cellulin is produced by islet cells, the peptide does not seem to be of importance for the regulation of insulin production by isolated pancreatic β-cells.
Key WordsPancreatic islet insulin secretion β-cellulin transforming growth factor
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