Nerve Growth Factor Neutralization Suppresses beta-Cell Proliferation Through Activin A and Betacellulin

作者：Gezginci Oktayoglu Selda^*; Karatug Ayse; Bolkent Sehnaz

来源：Pancreas, 2015, 44(2): 243-249.

DOI：10.1097/mpa.0000000000000243

• activin A
• betacellulin
• beta cell
• hyperglycemia
• nerve growth factor
• proliferation

Objective: 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 beta cells and the importance of these relations for beta-cell proliferation.
Methods: beta 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 beta 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.
Results: Nerve growth factor neutralization (1) reduced beta-cell proliferation, (2) decreased Act-A at gene expression and protein levels while increasing its secretion from beta cells, and (3) increased BTC at gene expression level while mildly decreasing its cellular protein level and secretion from beta cells. Nerve growth factor neutralization specifically affected beta cells of hyperglycemic rats.
Conclusions: These findings indicate that NGF is an important regulator for the synthesis and secretion of Act-A and BTC from the beta cells. Moreover, the results suggested that beta-cell proliferation decreased through NGF neutralization is possibly related to decreased BTC and increased Act-A secretion from beta cells of hyperglycemic rats.

• 出版日期2015-3