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 fact or (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 respon se to elevated glucose or potassium, but decreased in response to dibu tyryl cAMP. Moreover, steady-state levels of NGF mRNA are down-regulat ed by dibutyryl cAMP, which is opposite to the effect of cAMP on insul in release. NGF-stimulated changes in morphology and function are medi ated 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 m RNA are modulated by NGF and dibutyryl cAMP. Taken together, these fin dings suggest endocrine and autocrine roles for pancreatic beta-cell N GF, which, in turn, could be related to the pathogenesis of diabetes m ellitus where serum NGF levels are diminished.