Pancreatic β cells synthesize and secrete nerve growth factor

Pancreatic β cells synthesize and secrete nerve growth factor

Departments of ^*Biophysics and ^‡Cell Biology, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México DF 04510 Mexico

Communicated by Robert E. Forster, University of Pennsylvania School of Medicine, Philadelphia, PA (received for review January 16, 1998)

Abstract

Differentiation and function of pancreatic β cells are regulated by a variety of hormones and growth factors, including nerve growth factor (NGF). Whether this is an endocrine or autocrine/paracrine role for NGF is not known. We demonstrate that NGF is produced and secreted by adult rat pancreatic β cells. NGF secretion is increased in response to elevated glucose or potassium, but decreased in response to dibutyryl cAMP. Moreover, steady-state levels of NGF mRNA are down-regulated by dibutyryl cAMP, which is opposite to the effect of cAMP on insulin release. NGF-stimulated changes in morphology and function are mediated by high-affinity Trk A receptors in other mammalian cells. Trk A receptors are present in β cells and steady-state levels of Trk A mRNA are modulated by NGF and dibutyryl cAMP. Taken together, these findings suggest endocrine and autocrine roles for pancreatic β-cell NGF, which, in turn, could be related to the pathogenesis of diabetes mellitus where serum NGF levels are diminished.

Footnotes

↵ † T.R. and R.V. contributed equally to this work.
↵ § To whom reprint requests should be addressed. e-mail: mhiriart{at}ifcsun1.ifisiol.unam.mx.
ABBREVIATIONS:

NGF,

nerve growth factor;

dbcAMP,

dibutyryl cAMP;

RT,

reverse transcriptase;

GAPDH,

glyceraldehyde-3-phosphate dehydrogenase;

CM,

conditioned medium