Heterogeneities of the islets in the rabbit pancreas and the problem of ?paracrine? regulation of islet cells

Abstract

In addition to "external" signals conveyed by the circulation or the nervous system, the pancreatic islets obviously are regulated also by "internal" (intra-islet) signals, e.g. by the islet hormones: insulin (B-), glucagon (A-), and somatostatin (D-) cells are able to affect the secretion of the heterologous cell types. It is, however, unclear whether this functional cooperation between islet cells occurs by an intercellular route (paracrinia sensu strictore), by intra-islet "portal" vessels, or by the systemic circulation. These likely interactions are limited by islet anatomy. To identify the anatomical basis for the mutual functional relationships between the islet cells, islets of Langerhans in the rabbit pancreas were completely analyzed in immunostained serial semithin (0.5 micron) sections. The islets were found to be largely heterogenous. They were classified in three basic types: a) polycellular islets, composed of all established endocrine cells, and including two subtypes of islets, b) bicellular islets, containing only B- and A-cells or B- and D-cells, and c) monocellular islets, exclusively made up of B-cells. Concerning the modes of paracrine regulation of islet cells, the findings suggest primarily an endocrinous route of transport of the islet peptides to heterologous endocrine cells. The corresponding functional cooperation between islet cells probably is mediated rather by the systemic circulation than by intra-islet portal vessels.

The microanatomy of canine islets of Langerhans: implications for intra-islet regulation

“…J6rns et al 1988) and will, therefore, not be considered here in detail. In agreement with previous studies (e.g., Grube et al 1982;Rombout et al 1987;J6rns et al 1988), a certain proportion of glucagon (A-) and somatostatin (D-) cells exhibited concomitant immunoreactivities for pancreatic polypeptide. No attempt was made to register these cells separately during the systematic investigation.…”

“…Moreover, it is hardly conceivable that these heterogeneous microorgans all have a uniform vasculature. Indeed, there are indications in the literature that the microcirculation pattern of islets may be diverse in the same species (Grube and Bohn 1983;Grube and Weimann 1985;Yaginuma et al 1986;J6rns et al 1988). Although canine islets generally possess a dense capillary network, we have shown that the pattern of vascularization may vary even within the same islet (see Ferner 1952 for similar observations in human islets), eventually along with changes of the microtopology of the endocrine cell types.…”

“…In spite of this obvious lack of profound morphological information, conclusions concerning intra-islet regulatory mechanisms are based on the assumption that canine islets are only superficially dissimilar from those in rats ). On the other hand, previous studies have clearly revealed considerable heterogeneities of human and rabbit islets (Grube and Bohn 1983;Grube and Weimann 1985;J6rns et al 1988;Tr6ger 1991), indicating interspecies differences in islet microarchitecture.…”

Three-Dimensional Imaging of Intact Isolated Islets of Langerhans With Confocal Microscopy

“…Typically, after the initial staining and mounting of islets, we were able to produce three-dimensional images of individual islets within 30 min with the confocal microscope. The capability to rapidly determine the distribution of the various cell types throughout entire islets should be of immense benefit in determining the extent of heterogeneity observed between islets (12)(13)(14). Determination of islet anatomy, including the relationship of the different cell types to islet vasculature visualized with selective capillary stains, should provide an anatomical basis for possible paracrine interactions between different islet cell types.…”

“…islets (11)(12)(13)(14). Physical sectioning is not only time consuming but, more important, introduces technical difficulties and problems in interpreting three-dimensional structure because of the surface destruction that occurs during the sectioning process.…”