Nerve growth factor neutralization suppresses β-cell proliferation through activin A and betacellulin.
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 β cells and the importance of these relations for β-cell proliferation.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
From the Department of Biology, Faculty of Science, Istanbul University, Istanbul, Turkey.
Selda
S
Gezginci-Oktayoglu
Ayse
A
Karatug
Sehnaz
S
Bolkent
D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology*; D066259:Betacellulin / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D028322:Inhibin-beta Subunits / Q000235:genetics / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
D057134:Antibodies, Neutralizing; D066259:Betacellulin; C587853:Btc protein, rat; D012333:RNA, Messenger; C103008:inhibin beta A subunit; D020932:Nerve Growth Factor; D028322:Inhibin-beta Subunits