Nerve growth factor neutralization suppresses β-cell proliferation through activin A and betacellulin.

Abstract

The aim of this study was to investigate the effects of nerve growth factor (NGF) neutralization on synthesis and secretion of activin A (Act-A) and betacellulin (BTC) from primary β cells and the importance of these relations for β-cell proliferation. β Cells were isolated from euglycemic and streptozotocin-induced (75 mg/kg) hyperglycemic rats and treated with NGF neutralization antibody. The gene expression levels of Act-A and BTC in the primary β cells were evaluated using quantitative real-time polymerase chain reaction. The cellular and secreted levels of Act-A and BTC proteins were estimated using Western blot analysis. Nerve growth factor neutralization (1) reduced β-cell proliferation, (2) decreased Act-A at gene expression and protein levels while increasing its secretion from β cells, and (3) increased BTC at gene expression level while mildly decreasing its cellular protein level and secretion from β cells. Nerve growth factor neutralization specifically affected β cells of hyperglycemic rats. These findings indicate that NGF is an important regulator for the synthesis and secretion of Act-A and BTC from the β cells. Moreover, the results suggested that β-cell proliferation decreased through NGF neutralization is possibly related to decreased BTC and increased Act-A secretion from β cells of hyperglycemic rats.