Short- and long-term effects of beta-cellulin and transforming growth factor-alpha on beta-cell function in cultured fetal rat pancreatic islets.

The polypeptide beta-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 beta-cell. In this study, we investigated the short- and long-term actions of beta-cellulin, and the structurally related transforming growth factor-alpha (TGF-alpha), on beta-cell function in fetal rat pancreatic islets in vitro. We found that neither beta-cellulin nor TGF-alpha (10 nM each), in contrast to glucose (20 mM), acutely influenced beta-cell levels of cytosolic-free Ca2+. Additionally, whereas glucose markedly increased short-term (60-min) insulin release, neither beta-cellulin nor TGF-alpha (10 nM 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-alpha (10 nM), but not beta-cellulin (10 nM), at high (but not low) glucose concentrations. Conversely, the islet insulin content was not significantly affected by beta-cellulin or TGF-alpha at any glucose concentration tested. We conclude that, although beta-cellulin is produced by islet cells, the peptide does not seem to be of importance for the regulation of insulin production by isolated pancreatic beta-cells.