Nerve growth factor induces neuron-like differentiation of an insulin-secreting pancreatic beta cell line.
Nerve growth factor (NGF) is the best understood of a class of trophic proteins that are important for the survival of neurons and the elaboration of their characteristic processes. Here we demonstrate that RINm5F, a rat insulinoma cell line representing an early stage in pancreatic beta cell differentiation, expresses both the Trk and p75 NGF receptors and responds to NGF by extending neurite-like (neurofilament-containing) processes. NGF treatment of RINm5F cells also induces the expression of genes normally responsive to NGF in neurons, including the NGF-1A gene. Inasmuch as pancreatic beta cells arise from the embryonic endoderm, these results suggest that NGF may play a wider role during development than previously thought-a role not restricted to cells of neuroectodermal origin--and that endocrine and neuronal cells share a developmental pathway. The specific effect of NGF on an early pancreatic beta cell line also suggests that this neurotrophic factor might form the basis of a therapeutic treatment for some types of diabetes by inducing the proliferative differentiation of islet cells.
Department of Neurobiology, Harvard Medical School, Boston, MA 02115.
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M
Polak
R
R
Scharfmann
B
B
Seilheimer
G
G
Eisenbarth
D
D
Dressler
I M
IM
Verma
H
H
Potter
D000818:Animals; D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007340:Insulinoma; D007382:Intermediate Filaments / Q000187:drug effects / Q000648:ultrastructure; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D016716:PC12 Cells; D010190:Pancreatic Neoplasms; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
D007328:Insulin; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor