Proposal of a Neurosecretory System in the Pancreas

Abstract

Summary. The nerve fibers supplying the islets of the dog pancreas were examined by electron microscopy. Axons with swollen portions containing various types of synaptic vesicles, including a cholinergic type, two varieties of presumable aminergic type and a possible peptidergic type, rush to the pericapillary space to end there, whereas only a small part of them seem to terminate on the endocrine cells of the islet.Schwann cell cytoplasm invests the axons and often separates these from the endocrine cells. The terminal portions filled with vesicles usually become free of the Schwann sheath on the side facing the blood capillary. Here the neuronal secretions are believed to be released into the blood stream through the pored endothelium of the capillary.The neurosecretions, together with the islet hormones are distributed to the exocrine pancreas in high concentrations via the insulo-acinar portal system. It seems thus sufficient for the nerves to supply the islet in order to control the exocrine function of the pancreas.During the three decades since the establishment of the hypothalamo-hypophyseal neurosecretory system by BARGMANN (1949), the concept and criteria of neurosecretion have changed a great deal (LEDERIS, 1974;SANO, 1978). BARGMANN and SCHARRER (1951) regarded that stain-technologically demonstrable secretory granules are essential for a neurosecretory cell, but later this criterion had to be abandoned as newly discovered neurosecretory system producing and transporting releasing hormones from the hypothalamus to the hypophyseal portal vessels revealed no stainable granules. Recent advance in the knowledge of peptidergic neurons and of aminecontaining neurons occurring in different central and peripheral nervous tissues caused further confusion to the concept of neurosecretion. In agreement with SANO (1978), the last reliable criterion of neurosecretion (in higher vertebrates) must be that the neuronal secretions are released into the circulation and this is morphologically reflected in that the nerve terminals are not related to their target organ or cell but end in the perivascular (especially pericapillary) space.In the course of our electron microscope study of the dog pancreas, we recently noticed that numerous nerve terminals occur in the pericapillary spaces of the islet. Also by re-examining the electron micrographs which we produced for our previous *This paper is dedicated to the memory of the late Professor Wolfgang BARGMANN. 277

Ultrastructural simultaneous localization of vasoactive intestinal polypeptide immunoreactivity and the acetylcholine-like cation in rat endocrine pancreas.

“…The present findings do not exclude the possible release of neurosubstances into the blood (FUJITA and KOBAYASHI, 1979) and to the endothelial cells of the blood vessels. Particularly, ACh could control some function of the endothelial cells.…”

“…Ultrastructural observations (WATARI, 1968;KOBA-YASHI and FUJITA, 1969;SHORR and BLOOM, 1970;FUJITA and KOBAYASHI, 1979;RADKE and STACH, 1986) have revealed the presence of nerve endings in contact with endocrine cells and in close vicinity to the blood vessels. Physiological data showed a neural control of the secretion of endocrine cells (WOODS and PORTE, 1974).…”

“…VIP might also be subjected to neurosecretion into the blood capillaries of the islets (FUJITA and KOBAYASHI, 1979). Different types of nerve endings, among them cholinergic (WATARI, 1968;SHORR and BLOOM, 1970;FUJITA and KOBAYASHI, 1979) and peptidergic ones (FUJITA and KOBAYASHI, 1979) were characterized by the morphology of the synaptic vesicles they contained. The cholinergic mechanisms are presumed to be modulated by neuropeptides, including VIP (LUNDBERG et al, 1980;LEBLANC et al, 1987).…”

Fine structure of the neuro-insular complex type II in the cat.

“…Consequently, FUJITA modified his concept of paraneurons in assuming convergent differentiation, i.e., that these receptosecretory cells are derived from diverse origins (FUJITA and KOBAYASHI, 1979b); the endodermal origin of pancreatic endocrine cells is now out of dispute.…”

Pancreatic innervation in mouse development and β-cell regeneration

“…However, the subcellular VMAT2 + localization in these neurons during postnatal maturation implies that postganglionic sympathetic neurons may be physiologically able to accumulate and secrete noradrenaline during maturation of the endocrine pancreas. Pancreatic neurons do not form true synapses with islet cells (Fisher and Bourque 2001;Fujita and Kobayashi 1979;Serizawa et al 1979). While they contact target cells, to date there is no evidence to suggest the presence of postsynaptic densities that define the canonical synapse.…”