Immunohistochemical study of the developing endocrine pancreas of the opossum (Didelphis virginiana)

Cells immunoreactive for insulin, glucagon, somatostatin, bovine pancreatic polypeptide and 5-hydroxytryptamine are found in the pancreas of the newborn opossum and of all later stages examined. All immunoreactive cell types are present in primary and secondary islets and within elements of the exocrine pancreas. Cells immunoreactive for glucagon, bovine pancreatic polypeptide, somatostatin and 5-hydroxytryptamine generally are confined to the periphery of secondary (intralobular) islets, whereas insulin-immunoreactive cells occupy the central region. Endocrine cells within primary (interlobular) islets are randomly scattered. A small number of pancreatic-polypeptide-immunoreactive cells are reactive for the amine 5-hydroxytryptamine also, but the reverse is not observed. The endocrine pancreas continues to differentiate and develop throughout postnatal life and into adulthood. Little difference was observed between the head and tail regions of the opossum pancreas for the measurements made.     

Morphological changes in the human endocrine pancreas induced by chronic excess of endogenous glucagon.

The non-tumoral endocrine pancreas from a patient with elevated plasma levels of glucagon due to a malignant glucagonoma was studied immunocytochemically, ultrastructurally and morphometrically. Compared with normal pancreatic islets from control subjects, those of the pancreas from the patient with a glucagonoma showed an almost complete disappearance of A cells, a decrease in immunoreactive insulin in B cells associated with cytological features indicating enhanced synthesis and secretion of this hormone, and an increase in immunoreactive somatostatin and pancreatic polypeptide (PP) accompanied by unusually high numbers of D and PP cells. In addition, numerous B cells were found outside the islets, either forming micro-islets or scattered in the exocrine tissue (nesidioblastosis). The possible mechanisms involved in determining the changes in the secretory activity of B cells and the alterations in the cell composition of the islets are discussed.     

The endocrine cells in the gastroenteropancreatic system of the bowfin, Amia calva L.: an immunohistochemical, ultrastructural, and immunocytochemical analysis.

The gastroenteropancreatic (GEP) endocrine system of bowfin (Amia calva) was described using light and electron microscopy and immunological methods. The islet organ (endocrine pancreas) consists of diffusely scattered, mostly small islets and isolated patches of cells among and within the exocrine acini. The islets are composed of abundant, centrally located B cells immunoreactive to bovine and lamprey insulin antisera and D cells showing a widespread distribution and specificity to somatostatin antibodies. A and F cells are present at the very periphery of the islets and are immunoreactive with antisera against glucagon (and glucagon-like peptide) and several peptides of the pancreatic polypeptide (PP)-family, respectively. The peptides of the two families usually collocates within the same peripheral islet cells and are the most common immunoreactive peptides present in the extra-islet tissue. Immunocytochemistry and fine structural observations characterised the granule morphology for B and D cells and identified two cell types with granules immunoreactive to glucagon antisera. These two putative A cells had similar granules, which were distinct from either B or D cells, but one of the cells had rod-shaped cytoplasmic inclusions within cisternae of what appeared to be rough endoplasmic reticulum. The inclusions were not immunoreactive to either insulin or glucagon antisera. Only small numbers of cells in the stomach and intestine immunoreacted to antisera against somatostatin, glucagon, and PP-family peptides. The paucity of these cells was reflected in the low concentrations of these peptides in intestinal extracts. The GEP system of bowfin is not unlike that of other actinopterygian fishes, but there are some marked differences that may reflect the antiquity of this system and/or may be a consequence of the ontogeny of this system in this species.     

Ontogeny of immunoreactive glicentin in the human gastrointestinal tract and endocrine pancreas

The gestational time of appearance and distribution of immunoreactive glicentin was compared to that of immunoreactive glucagon in the gastrointestinal tract and endocrine pancreas of human fetuses, aged between 5 and 24 weeks, by an indirect immunoperoxidase method. With the glicentin antiserum No. R 64, the first immunoreactive cells were detected at the 10th week of gestation in the oxyntic mucosa and proximal small intestine, at the 8th week in the ileum and at the 12th week in the colon. In the endocrine pancreas, the first immunoreactive cells were observed as early as 8 weeks within the walls of the primitive pancreatic ductules. At a more advanced stage of development (12 weeks), they were found interspersed among the islet cell clusters and still later (16 weeks) inside the recognizable islets of Langerhans. With the glucagon antiserum No. GB 5667, no immunoreactive cells were demonstrated in the gastrointestinal tract whatever the age of the fetuses. In the endocrine pancreas, the first immunoreactive cells were observed at the 8th week of gestation in the pancreatic parenchyma. The distribution of glucagon-containing cells in the pancreas was similar to that of glicentin immunoreactivity throughout ontogenesis. In the pancreatic islets of one 18-week-old human fetus, the study of consecutive semithin sections treated by both antisera showed that the same cells were labelled. The significance of these findings concerning the role of glicentin as a glucagon precursor is discussed.     

Immunocytochemical investigation of the gastro-entero-pancreatic (GEP) neurohormonal peptides in the pancreas and gastrointestinal tract of the dogfish Squalus acanthias

The pancreas and gastrointestinal tract (GIT) of adults and of an embryonic stage of 11 cm long (about half the length of newborn fish) of the spiny dogfish, Squalus acanthias, were investigated immunocytochemically for the occurrence of the gastro-entero-pancreatic (GEP) neurohormonal peptides. In the pancreas of adult forms 5 endocrine cell types were seen, namely insulin-, somatostatin-, glucagon-, pancreatic polypeptide (PP)- and gastric inhibitory peptide (GIP)-immunoreactive cells. These cell types form scattered islets and were seen sometimes to surround small ducts. GIP-immunoreactivity cells did not occur in glucagon-containing cells. In the mucosa of GIT of adults 18 endocrine cell types were observed, viz. insulin-, somatostatin-, glucagon-, glicentin, PP-, polypeptide YY (PYY)-, vasoactive intestinal polypeptide (VIP)-, GIP-, gastrin C-terminus, CCK-, neurotensin N-terminus-, bombesin/gastrin releasing peptide (GRP)-, substance P-, enkephalin-, alpha-endorphin, beta-endorphin-, serotonin- and calcitonin immunoreactive cells. These cells occurred mostly in the intestine. All these cell types were of the open type, except glucagon- and glicentin-immunoreactive cells in the stomach, which seemed to be of the closed type. In the muscle layers and the submucosa, VIP and substance P- immunoreactive nerves and neurons were observed. In the pancreas of the dogfish embryo only 3 endocrine cell types could be demonstrated, namely insulin-, somatostatin- and glucagon-immunoreactive cells. In the mucosa of the GIT of the embryos studied 12 endocrine cell types were detected, viz. insulin-, somatostatin-, glucagon-, PP-, PYY-, VIP, GIP, gastrin C-terminus-, CCK-, neurotensin N-terminus-, enkephalin- and serotonin immunoreactive cells. The number of these cells, except that of PYY-immunoreactive cells, was lower than that of adults and in some cases their distribution did not correspond with that of adults.     

Polyhormonal aspect of the endocrine cells of the human fetal pancreas

Histological studies were performed on 30 pancreases obtained from normal human fetuses aged between the 9th and 38th week. For immunocytochemistry, the avidin-biotin-peroxidase method was used to identify and colocalise insulin, glucagon, somatostatin, pancreatic polypeptide and proliferating cell nuclear antigen. In the 9th week, cells containing all investigated peptides were present. During the fetal period, two populations of endocrine cells have been distinguished, Langerhans islets and freely dispersed cells. The free cells were polyhormonal, containing insulin, glucagon, somatostatin and pancreatic polypeptide, and were localised in the walls of pancreatic ducts throughout the whole gland. During the development of the islets we have observed four stages: (1) the scattered polyhormonal cell stage (9th–10th week), (2) the immature polyhormonal islet stage (11th–15th week), (3) the insulin monohormonal core islet stage (16th–29th week), in which zonular and mantle islets are observed, and (4) the polymorphic islet stage (from the 30th week onwards), which is characterised by the presence of monohormonal cells expressing glucagon or somatostatin. Bigeminal and polar islets also appeared during this last stage. The islets consisted of an insulin core surrounded by a thick (in the part developing from the dorsal primordium) or thin rim (part of the pancreas concerned with the ventral primordium) of intermingled mono- or dihormonal glucagon-positive or somatostatin-positive cells. The most externally located polyhormonal cells exhibited a reaction for glucagon, somatostatin and pancreatic polypeptide. Apart from the above-mentioned types of islets, all arrangements observed in earlier stages were present. Proliferating cell nuclear antigen-positive cells (single in the large islets and more numerous in the smaller ones) were predominantly observed in the outermost layer. Taken together our data indicate that, during the human prenatal development of the islet, endocrine cells are able to synthesise several different hormones. Maturation of these cells involved or depended on a change from a polyhormonal to a monohormonal state and is concerned with decreasing proliferative capacity. This supports the concept of a common precursor stem cell for the hormone-producing cells of the fetal human pancreas. Accepted: 1 June 1999     

Immunohistochemical study of the distribution of endocrine cells in the gastrointestinal tract of the camel (Camelus bactrianus)

The regional distribution and relative frequency of endocrine cells in the gastrointestinal tract of the camel, Camelus bactrianus, were investigated using immunohistochemical methods. Ten types of immunoreactive (IR) endocrine cells were identified in this study. Among these cell types, only serotonin- and somatostatin-IR cells were detected in almost all regions of the gastrointestinal tract. Most of the cell types showed peak density in the pyloric gland region. The others showed restricted distribution: gastrin, cholecystokinin (CCK), motilin, bovine pancreatic polypeptide (BPP), and (gastric) substance P in the stomach; gastrin, CCK, BPP, gastric inhibitory polypeptide (GIP), glucagon, peptide tyrosine tyrosine (PYY) and substance P in the small intestine; and CCK, motilin, BPP, and PYY in the large intestine. Fundamentally the distribution pattern of endocrine cells in the gastrointestinal tract of the camel is similar to that of cattle. The distribution and frequency of endocrine cells in the glandular sac region are the same as those of the cardiac gland.     

Ontogeny of the endocrine pancreas in sea bass (Dicentrarchus labrax)

Summary The development of the endocrine pancreas of the teleost sea bass (Dicentrarchus labrax, L.) was examined from hatching to 61 days, using the peroxidase-antiperoxidase technique for light microscopy. Mammalian and bonito insulin (mI and bI)-, salmo somatostatin-25 (SST-25)-, somatostatin-14 (SST-14a and b)-, glucagon-, bovine pancreatic polypeptide (PP)-, peptide tyrosine-tyrosine (PYY)- and salmo neuropeptide Y (NPY)-like immunoreactivity was demonstrated. Four ontogenetic stages were established according to the organization and immunostaining of the endocrine cells. One cell strand or primordial cord showing mI/bI- and SST-25/SST-14a-like immunoreactivity was first found at hatching in the dorsal epithelium of the anterior zone of the midgut (stage 1). One primitive islet, comprising outer SST-25/SST-14a- and inner mI/bI- and SST-14a/ SST-14b-immunoreactive cells, was found in 2- to 5-day-old larvae (stage 2). One single islet, in which glucagon-immunoreactive cells appear in the periphery, was found in larvae from 9 to 20 days after hatching (stage 3). One big islet containing, in addition, PP-immunoreactive cells in the outer region and slender cell processes which showed PYY-like immunoreactivity, was found from 25 to 61 days after hatching. During this period, primordial islets, composed of SST-25- and bI-immunoreactive cells, and clustered or isolated pancreatic endocrine cells, close to the pancreatic duct, as well as small and intermediate islets (secondary islets), in which glucagon, PP, PYY and NPY seem to be co-localized, were progressively found (stage 4). The origin of the endocrine pancreas of sea bass, and the ontogenetic and phylogenetic significance, are discussed.     

Ontogeny and the effect of aging on pancreatic polypeptide and peptide YY

Pancreatic polypeptide (PP) and peptide YY (PYY) are related neuroendocrine peptides that are expressed in specialized cells. PP is found around the time of birth in different species. PYY in mice and rats has been extensively studied. PYY is the first peptide hormone to appear in both the pancreas and the colon and is initially expressed together with all other pancreatic islet and gut hormones. This suggests that there is a PYY-producing endocrine progenitor cell, at least in rodents. Whether the same is true for other species is unknown. In chickens, however, pancreatic insulin and glucagon cells appear before PYY. After birth, PYY levels in rats and humans reflect adaptation to enteral feeding. Whereas PYY cells increase with age in rodents, no such changes have been found in humans.     

A light-microscopic immunocytochemical study of the endocrine pancreas in the Australian brush-tailed possum (Trichosurus vulpecula).

The endocrine pancreas of the Australian brush-tailed possum (Trichosurus vulpecula) was investigated by means of immunocytochemistry using the avidin-biotin-peroxidase technique. This was a light microscopic study using this established technique. Serial paraffin sections were stained individually with primary antibodies for glucagon, insulin, somatostatin, and pancreatic polypeptide (PP), showing the same islet. Cells immunoreactive to glucagon, insulin, somatostatin and PP were found in endocrine islets. PP cells appear to be scattered amidst the exocrine portion also. Insulin immunoreactive cells were located in the central region of islet, glucagon in the periphery, somatostatin in periphery and had elongated processes. PP cells were more sparse and located both in the periphery of islet and amidst the exocrine tissue. These results can then be related to a similar study in the same marsupial, but using the immunofluorescence technique and to studies in other marsupials such as grey kangaroo (Macropus fuliginosus) fat-tailed dunnart (Sminthopsis crasicaudata) and the American opossum (Didelphis virginiana). These investigations are part of a study in Australian mammals.     

大鼠胰腺嗜铬颗粒素A分布的免疫组织化学研究

本研究用ＡＢＣ免疫组织化学方法,在Ｂｏｕｉｎ液固定的常规石蜡切片上,观察了啥铬颗粒素Ａ在大鼠胰腺内分泌细胞内的定位和分布,并用相邻切片双标记法,观察了它与胰高血糖素、胰岛素、生长抑素的共存关系。结果发现,大鼠胰腺嗜铬颗粒素Ａ样免疫反应细胞主要分布于胰岛的周边部,胰腺外分泌部的导管和腺泡等处均未见ＣｇＡ祥物质存在。用相邻薄切片免疫显色技术证明,大鼠胰腺中ＣｇＡ样物质与胰高血糖素共存。结果提示,ＣｇＡ可能是胰腺内分泌细胞的一个新的标志物,在胰腺功能调节上发挥着重要作用。     

Impaired differentiation of endocrine and exocrine cells of the pancreas in transgenic mouse expressing the truncated type II activin receptor

Activin A is expressed in endocrine precursor cells of the fetal pancreatic anlage. To determine the physiological significance of activins in the pancreas, a transgenic mouse line expressing the truncated type II activin receptor under the control of beta-actin promoter was developed. Histological analyses of the pancreas revealed that the pancreatic islets of the transgenic mouse were small in size and were located mainly along the pancreatic ducts. Immunoreactive insulin was detected in islets, some acinar cells, and in some epithelial cells in the duct. In addition, there were abnormal endocrine cells outside the islets. The shape and the size of the endocrine cells varied and some of them were larger than islets. These cells expressed immunoreactive insulin and glucagon. In the exocrine portion, there were morphologically abnormal exocrine cells, which did not form a typical acinar structure. The cells lacked spatial polarity characteristics of acinar cells but expressed immunoreactive amylase, which was distributed diffusely in the cytoplasm. Plasma glucose concentration was normal in the transgenic mouse before and after the administration of glucose. The insulin content of the pancreas in transgenic and normal mice was nearly identical. These results suggest that activins or related ligands regulate the differentiation of the pancreatic endocrine and exocrine cells.     

Colocalization of glucagon-like peptide and glucagon immunoreactivities in pancreatic islets and intestine of salmonids

Summary Pancreatic islets of salmon contain at least two peptides of the glucagon family: 29-amino acid glucagon and 31-amino acid glucagon-like peptide (GLP). Both peptides were recently isolated from the pancreatic islets of coho salmon and sequenced (Plisetskaya et al. 1986). Antibodies generated against these two peptides and against human glucagon were used as immunocytochemical probes to investigate whether glucagon and GLP are processed in the same, or in different cell types in the pancreatic islets and the gut of salmon. Two salmonid species, rainbow trout and coho salmon, were studied. All islet A-cells in the two species were immunoreactive toward both anti-salmon (s)-glucagon and anti-s-GLP. Similar colocalization of glucagon and GLP immunoreactivities was found in open-type endocrine cells in mucosae of the small intestine (including the pyloric coecae) and the large intestine close to the vent of rainbow trout. None of the antibodies stained mucosal cells of the body of the stomach. These results suggest that in the pancreas and the gut of salmonid fish the same cells produce both glucagon and GLP. These peptides are most likely the products of a single gene coding for the preproglucagon sequence.     

Immunocytochemical demonstration of vertebrate neuropeptides in the earthworm Lumbricus terrestris (Annelida,Oligochaeta)

Summary The localisation and distribution of 10 vertebrate-derived neuropeptides in the earthworm, Lumbricus terrestris, have been determined by an indirect immunofluorescence technique. The peptides are pancreatic polypeptide (PP), peptide tyrosine tyrosine (PYY), neuropeptide Y (NPY), glucagon (C-terminal), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), gastrinreleasing peptide (GRP), calcitonin gene-related peptide (CGRP), neurotensin (NT), and met-enkephalin. For 6 of the peptides — PYY, NPY, PHI, glucagon, GRP and CGRP — this is the first demonstration of their presence in any annelid, and NT has not previously been described in an oligochaete. Cell bodies and nerve fibres immunoreactive to the 10 peptides occur throughout the CNS. In the PNS, epidermal sensory cells displayed immunoreactivities to PP and PYY, and PP-, PYY-, NPY-, PHI- and GRP-like immunoreactivities occurred in nerve fibres supplying the main body muscles. Nerve fibres immunoreactive to PP and PYY are also associated with the innervation of the gut (pharynx, oesophageal glands, and mid and posterior regions of the intestine). No endocrine cells immunoreactive for any of the antisera tested could be identified in the gut epithelium, suggesting that dual location of peptides in the brain and gut epithelium is a phenomenon that occurred at a later stage in evolution. No immunoreactive elements were detected in any of the organs and ducts of the reproductive and excretory systems.     

Distribution and frequency of endocrine cells in the pancreas of the ddY mouse: an immunohistochemical study

The regional distribution and frequency of pancreatic endocrine cells in ddY mice were studied by an immunohistochemical (peroxidase anti-peroxidase; PAP) method using four types of specific antisera against insulin, glucagon, somatostatin and human pancreatic polypeptide (hPP). In the pancreatic islets, most of insulin-immunoreactive (IR) cells were located in the central portion. Most of glucagon- and somatostatin-IR cells were observed in peripheral regions although a somewhat smaller number of cells were also located in the central regions. HPP-IR cells were randomly distributed throughout the entire islets. In the exocrine pancreas, insulin-, glucagon-, somatostatin- and hPP-IR cells were detected; they occurred mainly among the exocrine parenchyma as solitary cells. Cell clusters consisted of only insulin- or only glucagon-IR cells and were distributed in the pancreas parenchyma as small islets. In addition, insulin- and glucagon-IR cells were also demonstrated in the pancreatic duct regions. Insulin-IR cells were located in the epithelium and sub-epithelial connective tissue regions as solitary cells and/or clusters (3-4 cells), and glucagon-IR cells were mainly located in the epithelium as solitary cells. Overall, there were 63.89+/-5.39% insulin-, 26.52+/-3.55% glucagon-, 7.25+/-2.83% somatostatin- and 1.90+/-0.58% hPP-IR cells. In conclusion, some strain-dependent characteristic distributional patterns of pancreatic endocrine cells were found in the ddY mouse.     

Ontogeny of rat pancreatic polypeptide (PP) cells

Summary Cells storing pancreatic polypeptide (PP) appear in rat pancreas at the time of parturition, much later than insulin and glucagon cells. At this stage, the pancreatic polypeptide (PP) cells occur scattered in the exocrine parenchyma and in the islets. Subsequently, 5–7 days postnatally, an abrupt increase in the number of PP cells occurs. At this stage, they are fairly numerous in the islets and comparatively rare in the exocrine parenchyma. Not until 8–10 days after birth is the number of PP cells similar to that in the adult pancreas. A few PP cells were seen in the antral mucosa during the first 10 days after birth. They were not seen elsewhere in the gut.     

Immunohistochemical localization of human kallikreins 6 and 10 in pancreatic islets

Tissue kallikreins are thought to be present in the pancreatic islets of Langerhans and to aid in the conversion of proinsulin to insulin. In recent immunohistochemical studies, we observed strong staining of the newly identified human kallikreins 6 and 10 (hK6 and hK10) in the islets of Langerhans. Here, we examine hK6 and hK10 immunoexpression in different types of islet cells of the endocrine pancreas, in order to obtain clues for hK6 and hK10 function in these cells. Ten cases of normal pancreatic tissue, two cases of nesidioblastosis, five insulin-producing tumours and one case of multiple endocrine neoplasia 1 syndrome, containing an insulin-, a somatostatin- and several glucagon-producing tumours, as well as tiny foci of endocrine dysplasia with different predominance of the secreted hormones (mainly glucagon and pancreatic polypeptide) were included in the study. A streptavidin–biotin–peroxidase and an alkaline phosphatase protocol, as well as a sequential immunoenzymatic double staining method were performed, using specific antibodies against hK6, hK10, insulin, glucagon, somatostatin, pancreatic polypeptide, and serotonin. hK6 and hK10 immunoexpression was observed in the islets of Langerhans, including the pancreatic polypeptide-rich islets, in the normal pancreas. Scattered hK6 and hK10 positive cells were localized in relationship with pancreatic acinar cells. In the exocrine pancreas, a cytoplasmic and/or brush border hK6 and hK10 immunoexpression was observed in the median and small sized pancreatic ducts, while the acinar cells were negative. Foci of nesidioblastosis and endocrine dysplasia expressed both kallikreins. hK6 and hK10 were also strongly and diffusely expressed throughout all insulin-, glucagon- and somatostatin-producing tumours. The double staining method revealed co-localization of each hormone and hK6/hK10 respectively, in the same cellular population, in the normal as well as in the diseased pancreas. Our results support the view that hK6 and hK10 may be involved in insulin and other pancreatic hormone processing and/or secretion, as well as in physiological functions related to the endocrine pancreas.     

Immunocytochemical investigation of the gastro-enteropancreatic (GEP) neurohormonal peptides in the pancreas and gastrointestinal tract of the dogfishSqualus acanthias

Summary The pancreas and gastrointestinal tract (GIT) of adults and of an embryonic stage of 11 cm long (about half the length of newborn fish) of the spiny dogfish,Squalus acanthias, were investigated immunocytochemically for the occurrence of the gastro-entero-pancreatic (GEP) neurohormonal peptides. In the pancreas of adult forms 5 endocrine cell types were seen, namely insulin-, somatostatin-, glucagon-, pancreatic polypeptide (PP)- and gastric inhibitory peptide (GIP)-immunoreactive cells. These cell types form scatterd islets and were seen sometimes to surround small ducts. GIP-immunoreactivity cells did not occur in glucagon-containing cells. In the mucosa of GIT of adults 18 endocrine cell types were observed, viz. insulin-, somatostatin-, glucagon-, glicentin-, PP-, polypeptide YY (PYY)-, vasoactive intestinal polypeptide (VIP)-, GIP-, gastrin C-terminus, CCK-, neurotensin N-terminus-, bombesin/gastrin releasing peptide (GRP)-, substance P-, enkephalin-, -endorphin, -endorphin-, serotonin- and calcitonin immunoreactive cells. These cells occurred mostly in the intestine. All these cell types were of the open type, except glucagon- and glicentin-immunoreactive cells in the stomach, which seemed to be of the closed type. In the muscle layers and the submucosa, VIP and substance P-immunoreactive nerves and neurons were observed. In the pancreas of the dogfish embryo only 3 endocrine cell types could be demonstrated, namely insulin-, somatostatin- and glucagon-immunoreactive cells. In the mucosa of the GIT of the embryos studied 12 endocrine cell types were detected, viz. insulin-, somatostatin-, glucagon-, PP-, PYY-, VIP, GIP, gastrin C-terminus-, CCK-, neurotensin N-terminus-, enkephalin- and serotonin immunoreactive cells. The number of these cells, except that of PYY-immunoreactive cells, was lower than that of adults and in some cases their distribution did not correspond with that of adults.     

Immunocytochemical localization of hormone-producing cells within the pancreatic islets of the rainbow trout (Salmo gairdneri)

Summary A histological study of the pancreatic islets in rainbow trout, Salmo gairdneri, was undertaken in which polypeptide hormone-producing cells were localized, using immunocytochemical staining techniques. Four different celltypes were identified in this manner. These were the insulin, somatostatin, pancreatic polypeptide and glucagon/gastric inhibitory polypeptide (GIP) cells. The glucagon/GIP cell was designated thus as antisera to both hormones crossreacted with a common population of cells. A fifth cell-type, commonly referred to as a clear cell, was also identified although its secretory product is as yet undetermined. These functional cell types were compared to the standard tinctorial properties of pancreatic endocrine cells. The relationships of the various cell types with each other was also observed.