Pancreatic beta cells synthesize and secrete nerve growth factor.
Differentiation and function of pancreatic beta 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 beta 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 beta 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 beta-cell NGF, which, in turn, could be related to the pathogenesis of diabetes mellitus where serum NGF levels are diminished.
Rosenbaum
T
T
Department of Biophysics, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México DF 04510 Mexico.
Vidaltamayo
R
R
Sánchez-Soto
M C
MC
Zentella
A
A
Hiriart
M
M
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000378:metabolism*; D016716:PC12 Cells; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics
D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; D003994:Bucladesine; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D005947:Glucose