Distribution Of Endocrine Cells Research Articles

Thyroid Hormone Levels Correlate With the Maturation of Implanted Pancreatic Endoderm Cells in Patients With Type 1 Diabetes.

Macroencapsulated pancreatic endoderm cells (PECs) can reverse diabetes in rodents and preclinical studies revealed that thyroid hormones in vitro and in vivo bias PECs to differentiate into insulin-producing cells. In an ongoing clinical trial, PECs implanted in macroencapsulation devices into patients with type 1 diabetes were safe but yielded heterogeneous outcomes. Though most patients developed meal responsive C-peptide, levels were heterogeneous and explanted grafts had variable numbers of surviving cells with variable distribution of endocrine cells. We measured circulating triiodothyronine and thyroxine levels in all patients treated at 1 of the 7 sites of the ongoing clinical trial and determined if thyroid hormone levels were associated with the C-peptide or glucagon levels and cell fate of implanted PECs. Both triiodothyronine and thyroxine levels were significantly associated with the proportion of cells that adopted an insulin-producing fate with a mature phenotype. Thyroid hormone levels were inversely correlated to circulating glucagon levels after implantation, suggesting that thyroid hormones lead PECs to favor an insulin-producing fate over a glucagon-producing fate. In mice, hyperthyroidism led to more rapid maturation of PECs into insulin-producing cells similar in phenotype to PECs in euthyroid mice. These data highlight the relevance of thyroid hormones in the context of PEC therapy in patients with type 1 diabetes and suggest that a thyroid hormone adjuvant therapy may optimize cell outcomes in some PEC recipients.

Distribution and localization of endocrine cells in the digestive system of chukar partridge (Alectoris chukar)

There are different types of endocrine cells that are located in the gastrointestinal system of birds and mammals. In birds, the digestive system anatomically completes the formation in the embryonic period, and in the period after hatching. Morphological and physiological differences with nutrition are formed and functionalized. The present study aimed to evaluate immunohistochemical distribution and localization of endocrine cells in the digestive tract of chukar partridges (Alectoris chukar) using antisera against serotonin, somatostatin, gastrin, and glucagon. In this study, after 20 chukar partridges were slaughtered, organs of the digestive system were obtained and stained for immunohistochemical analysis. In our results, various densities of glucagon, gastrin serotonin, and somatostatin positive cells in the proventriculus and small intestine were found, but only serotonin positive cells were detected in the ventriculus of chukar partridges. In conclusion, the results showed the relative frequency and distribution of some endocrine cells in the gastrointestinal tract of chukar partridge. A comparison of endocrine cell distribution in other bird species is an important topic to understand the digestive physiology for future investigation.

Structural and functional polarisation of human pancreatic beta cells in islets from organ donors with and without type 2 diabetes

Aims/hypothesisWe hypothesised that human beta cells are structurally and functional polarised with respect to the islet capillaries. We set out to test this using confocal microscopy to map the 3D spatial arrangement of key proteins and live-cell imaging to determine the distribution of insulin granule fusion around the cells.MethodsHuman pancreas samples were rapidly fixed and processed using the pancreatic slice technique, which maintains islet structure and architecture. Slices were stained using immunofluorescence for polarity markers (scribble, discs large [Dlg] and partitioning defective 3 homologue [Par3]) and presynaptic markers (liprin, Rab3-interacting protein [RIM2] and piccolo) and imaged using 3D confocal microscopy. Isolated human islets were dispersed and cultured on laminin-511-coated coverslips. Live 3D two-photon microscopy was used on cultured cells to image exocytic granule fusion events upon glucose stimulation.ResultsAssessment of the distribution of endocrine cells across human islets found that, despite distinct islet-to-islet complexity and variability, including multi-lobular islets, and intermixing of alpha and beta cells, there is still a striking enrichment of alpha cells at the islet mantle. Measures of cell position demonstrate that most beta cells contact islet capillaries. Subcellularly, beta cells consistently position polar determinants, such as Par3, Dlg and scribble, with a basal domain towards the capillaries and apical domain at the opposite face. The capillary interface/vascular face is enriched in presynaptic scaffold proteins, such as liprin, RIM2 and piccolo. Interestingly, enrichment of presynaptic scaffold proteins also occurs where the beta cells contact peri-islet capillaries, suggesting functional interactions. We also observed the same polarisation of synaptic scaffold proteins in islets from type 2 diabetic patients. Consistent with polarised function, isolated beta cells cultured onto laminin-coated coverslips target insulin granule fusion to the coverslip.Conclusions/interpretationStructural and functional polarisation is a defining feature of human pancreatic beta cells and plays an important role in the control of insulin secretion.Graphical abstract

Morphological and Immunohistochemical Study on the Distribution of Endocrine Cells in the Gastrointestinal Tract of Partridge, Alectoris chukar

Morphological and Immunohistochemical Study on the Distribution of Endocrine Cells in the Gastrointestinal Tract of Partridge, Alectoris chukar

Metabolome modulatory effects of Kigelia africana (Lam.) Benth. fruit extracts on oxidative stress, hyperlipidaemic biomarkers in STZ-induced diabetic rats and antidiabetic effects in 3T3 L1 adipocytes.

The management of diabetes is considered a global problem, and a cure is yet to be discovered. This study investigated the modulatory effect of Kigelia africana fruit on oxidative stress and hyperlipidaemic biomarkers in STZ-induced diabetic rats, profiled phytoconstituents using GC-TOF-MS and evaluated antidiabetic effects on 3T3 L1 adipocytes. Thirty male Wistar rats (120-150g) were divided into six groups (n=5). Diabetes was induced by a single intraperitoneal injection of STZ (60mg/kg) and treated with 100, 200 and 400 of hexane fraction of KA for 28days. Immunohistochemical evaluation was carried out using avidin-biotin immunoperoxidase (ABI) method. Catalase and SOD activities as well as the levels of total protein, albumin, bilirubin, triglyceride, cholesterol, and high-density lipoprotein were measured. The expressions of oxidative stress and hyperlipidaemic biomarkers alongside fasting blood glucose concentrations were remarkedly decreased in KA-treated diabetic rats. Moreover, there was a significant increase in endocrine cell distribution, area covered with increase in β-cell mass, composition and morphology of KA-treated animals. Additionally, there was constant up-regulation in 3T3 L1 adipocytes due to the presence of phytoconstituents. Kigelia africana fruit can act as a modulatory agent due to its ameliorative effects against oxidative stress.

Regional and mucosal distributions of some intestinal immunoreactive endocrine cells in New Zealand white rabbit (Oryctolagus cuniculus L.).

The aim of this study was to detect the regional and mucosal distribution of endocrine cells that secrete gulcagon, somatostatin, Chyholecystokinin-8 (CCK-8), serotonin, secretin, substance P (SP) and histamine in the small and large intestine of New Zealand white rabbit (Oryctolagus cuniculus L.) using immunohistochemical peroxidase-antiperoxidase (PAP) method. It was found that most of the immunoreactive (IR) endocrine cells, which are oval- or spindle-shaped, are spotted in the basal parts of the relevant glands. It was noticed that cells in the lamina epithelialis of small and large intestine is linked to the lumen and that the cells in their glands cannot reach the lumen. Immunoreactive cells for glucagon, somatostatin, serotonin, secretin and SP were identified in lamina epithelialis of the small and large intestine. It was seen that secretin, SP and histamine-IR cells are rarely deployed throughout the intestinal tract. It was determined that somatostatin-IR cells were identified throughout the intestinal tract. In conclusion, the immunohistochemical study shows that gastrointestinal tract of this species contained different types of endocrine cells similar to those found in other vertebrate species. However, some species-dependent unique distributions and frequencies of endocrine cells were also observed in the present study.

Evaluation of immunohistochemical staining for glucagon in human pancreatic tissue

Immunohistochemistry (IHC) and immunofluorescence (IF) staining techniques are important diagnostic tools of anatomic pathology in the clinical setting and widely used analytical tools in research laboratories. In diabetes research, they are routinely used for the assessment of beta- and alpha-cell mass, for assessment of endocrine cell distribution within the pancreas, for evaluation of islet composition and islet morphology. Here, we present the evaluation of IHC techniques for the detection of alpha-cells in human pancreatic tissue. We compared the Horse Radish Peroxidase (HRP)-based method utilizing DAB Peroxidase Substrate to the Alkaline Phosphatase (AP)-based method utilizing Vector Red substrate. We conclude that HRP–DAB staining is a robust and reliable method for detection of alpha-cells using either rabbit polyclonal or mouse monoclonal anti-glucagon antibodies. However, AP-Vector Red staining should be used with caution, because it is affected by the dehydration with ethanol and toluene preceding the mounting of slides with Permount mounting medium. When AP-Vector Red is a preferable method for alpha-cell labeling, slides should be mounted using aqueous mounting medium or, alternatively, they could be air-dried before permanent mounting

Relative distribution of gastrin-, CCK-8-, NPY- and CGRP-immunoreactive cells in the digestive tract of dorado (Salminus brasiliensis).

The endocrine cells (ECs) of the gastrointestinal mucosa form the largest endocrine system in the body, not only in terms of cell numbers but also in terms of the different produced substances. Data describing the association between the relative distributions of the peptide-specific ECs in relation to feeding habits can be useful tools that enable the creation of a general expected pattern of EC distribution. We aimed to investigate the distribution of ECs immunoreactive for the peptides gastrin (GAS), cholecystokinin (CCK-8), neuropeptide Y (NPY), and calcitonin gene-related peptide (CGRP) in different segments of the digestive tract of carnivorous fish dorado (Salminus brasiliensis) by using immunohistochemistry procedures. The distribution of endocrine cells immunoreactive for gastrin (GAS), cholecystokinin (CCK-8), neuropeptide Y (NPY), and calcitonin gene-related peptide (CGRP) in digestive tract of dorado S. brasiliensis was examined by immunohistochemistry. The results describe the association between the distribution of the peptide-specific endocrine cells and feeding habits in different carnivorous fish. The largest number of endocrine cells immunoreactive for GAS, CCK-8, and CGRP were found in the pyloric stomach region and the pyloric caeca. However, NPY-immunoreactive endocrine cells were markedly restricted to the midgut. The distribution pattern of endocrine cells identified in S. brasiliensis is similar to that found in other carnivorous fishes.

Distribution of endocrine cells in the digestive tract of Alligator sinensis during the active and hibernating period.

The digestive tract is the largest endocrine organ in the body; the distribution pattern of endocrine cells varies with different pathological and physiological states. The aim of the present study was to investigate the distributed density of 5-hydroxytryptamine (5-HT), gastrin (GAS), somatostatin (SS) and vasoactive intestinal peptide (VIP) immunoreactive (IR) cells in the digestive tract of Alligator sinensis during the active and hibernating period by immunohistochemical (IHC) method. The results indicated that 5-HT-IR cells were distributed throughout the entire digestive tract, which were most predominant in duodenum and jejunum. The density increased significantly in stomach and duodenum during hibernation. GAS-IR cells were limited in small stomach and small intestine. The density decreased significantly in small stomach during hibernation, while increased in duodenum. What's more, most of the endocrine cells in duodenum were generally spindle shaped with long cytoplasmic processes ending in the lumen during hibernation. SS-IR cells were limited in stomach and small stomach. The density increased in stomach while decreased in small stomach during hibernation, meanwhile, fewer IR cells occurred in small intestine. VIP-IR cells occurred in stomach and small stomach. The density decreased in small stomach, while increased in stomach during hibernation. These results indicated that the endocrine cells in different parts of digestive tract varied differently during hibernation, their changes were adaptive response to the hibernation.

Immunohistochemical distribution of glucagon -, insulin -, somatostatin -, gastrin-, and serotonin-containing cells in the pancreas of the Van cat

The regional distribution, relative frequency, and appearance of glucagon (A-cell)-, insulin (B-cell)-, somatostatin (D-cell)-, gastrin (G-cell)-, and serotonin (EC-cell)-secreting cells in the endocrine and exocrine pancreas of Van cats were examined using the immunohistochemistry method. Glucagon immunopositive A-cells were principally found in the central region of the islets of Langerhans, while insulin immunopositive B-cells were located in the periphery of the pancreatic islets. Moreover, several A- and B-cells were observed as only single cells or clusters of 2 to 3 immunopositive cells in the exocrine parenchyma and the pancreatic duct epithelium. Somatostatin and gastrin immunopositive reactivities were negligible in the peripheral regions of the pancreatic islets of Langerhans and in the exocrine parenchyma. However, serotonin-immunopositive EC-cells were observed in neither the endocrine islets nor any other sites of the tissue. The existence, regional distribution, and relative frequency of A-, B-, D-, G- and EC-cells in the pancreas of Van cats have been analyzed in this study for the first time. The immunopositivity and distribution of endocrine cells in the Van cat pancreas were determined to be partially different from those of other carnivorous species such as dogs and other cats.

Immunohistochemical Study of α- and β-Cell Distribution in Human Pancreatic Langerhans Islets of Various Types

Various types of insulin- and glucagon-containing endocrine cell distribution were found by double staining with antibodies to insulin and glucagon in the pancreatic autopsy material from subjects without carbohydrate metabolism disorders. The cell composition of the islets and their morphogenetic maturity depended on the vascularization degree. Insulin-containing cells predominated in small clusters of endocrine cells and in islets with few capillaries, while glucagon predominated in large islets with rich vascularization. A scheme of development and differentiation of Langerhans islets in the adult human pancreas was presented.

Morphologic characterization and distribution of endocrine cells in the large intestine of the opossum Didelphis aurita (Wied-Neuwied, 1826)

This study was designed to investigate the morphology and distribution of argyrophil, argentaffins, and insulin-immunoreactive endocrine cells in the large intestine of the opossum Didelphis aurita. Fragments of the large intestine of 10 male specimens of the opossum D. aurita were collected, processed, and submitted for histochemistry, immunohistochemistry, and scanning electron microscopy. The tunics of the large intestine of D. aurita presented morphological characteristics that have already been described for eutherian mammals. The morphometric data showed that the inner circular layer of all portions and regions analyzed is thicker relative to the longitudinal layer, and these layers in the rectum are thicker compared to the cecum and ascending colon. The majority of mucus-secreting cells have acid and neutral mucins, suggesting that the production of mucus is mixed. The number of these cells increases in the region of the cecum toward the rectum. Important findings include the occurrence of argyrophil, argentaffins, and insulin-immunoreactive endocrine cells in all segments of the large intestine of the opossum (D. aurita). To the best of our knowledge, this is the first report about the presence of insulin-immunoreactive endocrine cells in the large intestine of the opossum (D. aurita).

On the role of lateral stabilization during early patterning in the pancreas

The cell fate decision of multi-potent pancreatic progenitor cells between the exocrine and endocrine lineages is regulated by Notch signalling, mediated by cell-cell interactions. However, canonical models of Notch-mediated lateral inhibition cannot explain the scattered spatial distribution of endocrine cells and the cell-type ratio in the developing pancreas. Based on evidence from acinar-to-islet cell transdifferentiation in vitro, we propose that lateral stabilization, i.e. positive feedback between adjacent progenitor cells, acts in parallel with lateral inhibition to regulate pattern formation in the pancreas. A simple mathematical model of transcriptional regulation and cell-cell interaction reveals the existence of multi-stability of spatial patterns whose simultaneous occurrence causes scattering of endocrine cells in the presence of noise. The scattering pattern allows for control of the endocrine-to-exocrine cell-type ratio by modulation of lateral stabilization strength. These theoretical results suggest a previously unrecognized role for lateral stabilization in lineage specification, spatial patterning and cell-type ratio control in organ development.

Pancreatic islet cell phenotype and endocrine function throughout diabetes development in non-obese diabetic mice

Type 1 diabetes (T1D) results from a T cell dependent, autoimmune destruction of insulin producing beta cells in pancreatic islets of Langerhans, which results in insulin deficiency despite attempts at beta cell replacement by the emergence of newly-differentiated beta cells throughout T1D development. The origin of these cells has been difficult to assess as these are rapidly destroyed by the underlying autoimmunity. The identification of islets of Langerhans is typically assessed by either immunochemistry or immunofluorescence using antibodies directed against the different signature hormones and surface markers of various endocrine cells . However, the limited number of markers that can be used simultaneously and the uneven spatial distribution of endocrine cells within islets, limit the use of these histological analyses. To circumvent these caveats, we developed a novel approach using multi-parametric flow cytometry to assess the phenotype and function of pancreatic islet cell populations throughout T1D development. Using such strategy, we show that while beta cells undergo autoimmune destruction, insulin-producing cells arise from trans-differentiated alpha or delta cells, an outcome that was not solely the result of beta cell self-renewal. Moreover, we show that CD4+T cell-mediated inflammation correlates with the emergence of this insulin-producing beta cell-like cell.

Quantitative Analysis of Pancreatic Polypeptide Cell Distribution in the Human Pancreas

The pancreatic islet is mainly composed of beta-, alpha- and delta-cells with small numbers of pancreatic polypeptide (PP) and epsilon cells. It is known that there is a region in the head of the pancreas that is rich in PP-cells. In the present study, we examined the distribution of PP-cells, and assessed the influence of the PP-cell rich region to quantify the total islet mass. Pancreatic tissues were collected from donors with no history of diabetes or pancreatic diseases (n = 12). A stereological approach with a computer-assisted large-scale analysis of whole pancreatic sections was applied to quantify the entire distribution of endocrine cells within a given section. The initial whole pancreas analysis showed that a PP-cell rich region was largely restricted to the uncinate process with a clear boundary. The distinct distribution of PP-cells includes irregularly shaped clusters composed solely of PP-cells. Furthermore, in the PP-cell rich region, beta- and alpha-cell mass is significantly reduced compared to surrounding PP-cell poor regions. The results suggest that the analysis of the head region should distinguish the PP-cell rich region, which is best examined separately. This study presents an important implication for the regional selection and interpretation of the results.

Gastric histopathological findings and ghrelin expression in morbid obesity

The role of Ghrelin, also known as the appetite hormone, is not fully explained in the development of morbid obesity. Plasma Ghrelin level is low in obese and high in slim subjects. Ghrelin-expressing cells were investigated histopathologically in the stomach of morbid obese patients in this study. Tissue Ghrelin expression was also compared with various parameters such as the distribution of endocrine cells, age, gender, body mass index, preoperative plasma Ghrelin level and presence of accompanying diseases. The study included 33 morbidly obese patients, and 8 non-obese control patients. Plasma Ghrelin levels were measured preoperatively. Sleeve gastrectomy resection materials of 33 cases were evaluated with histopathological and immunohistochemical (Ghrelin and Chromogranin-A) techniques. The results were statistically evaluated by nonparametric tests. Histopathological findings observed in sleeve gastrectomy resection materials were interstitial lymphocytic infiltration (63.6%), hyperplasia of lymphoid follicles in the lamina propria (60.7%) and microvesiculation / dilatation of parietal cells (57.6%). The number of Ghrelin immunopositive cells in the gastric mucosa in females was significantly higher compared to males (p=0,007). Additionally, the number of Ghrelin immunopositive cells was significantly higher at the fundus-proximal corpus compared to the distal corpus of the stomach (p=0.0001). No significant correlation was found between Ghrelin-chromogranin immunopositive endocrine cell distribution and preoperative plasma Ghrelin levels and endocrine cell hyperplasia. Our study confirms that Ghrelin producing cells are most dense in the proximal stomach. Increased number of Ghrelin expressing cells in the gastric mucosa in females compared to males suggests that gender may also be a factor in determining the method for treatment of morbid obesity.

Endocrine cells and nerve ganglia of the small intestine of the Opossum Didelphis aurita Wied-Neuwied, 1826 (Mammalia: Didelphidae)

The nervous and endocrine systems jointly control intestinal movements, secretions of their glands and also participate of the processes of nutrient digestion and absorption. Therefore, the central objective of this study was to verify the existence of a possible relationship between the number of nervous cells and ganglia of the submucosal and myenteric plexuses and the number of endocrine cells in the small intestine of adult D. aurita. The utilized staining techniques were Grimelius, modified Masson-Fontana, direct immunoperoxidase and H-E. Argyrophillic, argentaffin and insulin immunoreactive endocrine cells do not numerically vary between the initial, mid and final regions of the duodenum, jejunum and ileum (P>0.05), except for argyrophillic cells in the jejunum (P>0.05). No numerical relationship has yet been verified between the number of nerve ganglia and endocrine cells, and also between nervous and endocrine cells. We recommended the use of new immunohistochemical techniques to confirm the numerical correlation between the nervous and endocrine systems in the small intestine. The morphology and distribution of endocrine cells and the nerve ganglia studied were similar to those encountered in eutherian mammals.

An immunohistochemical study on the distribution of endocrine cells in the digestive tract of gray goose (Anser anser)

The objective of this study was to investigate the morphology and the distribution of 5-hydroxytryptamine (5-HT), somatostatin (SS), gastrin (Gas), glucagon (Glu), and substance P immunoreactive (IR) cells in the digestive tract of gray goose by the immunohistochemical streptavidin-peroxidase method. The samples were taken from 10 healthy adult gray geese. The results showed that 5 kinds of IR cells were mainly distributed between the mucous epithelium and intestinal gland. The number of 5-HT-IR cells was highest in the rectum and duodenum, but none were observed in the pylorus. SS-IR cells appeared in great numbers in the pylorus, duodenum, and cecum; however, they were not found in esophagus. Gas-IR cells were mainly distributed in the glandular stomach and jejunum. Glu-IR cells appeared in small numbers in the glandular stomach, duodenum, and jejunum, but were not detected in other tissues. Substance P-IR cells were located in the jejunum, cecum, and rectum. Analysis of the present study showed that the distribution and morphological features of these 5 different endocrine cells were related to the feeding habits and metabolism in the digestive tract of the gray goose.

Distributions of the endocrine cells in the gastrointestinal tract of nectarivorous and sanguivorous bats: A comparative immunocytochemical study

The present study was conducted to clarify the influence of feeding habits on regional distribution and relative frequency of endocrine cells secreting cholecystokinin (CCK), gastrin (GAS), serotonin (5-HT) and enteroglucagon (GLUC) in the nectarivorous Anoura geoffroyi and Glossophaga soricina and the sanguivorous Desmodus rotundus bats of the Phyllostomidae family, by specific immunohistochemical methods. The regional distribution and frequency of the different types of endocrine cells varied according to their location in the GIT. 5-HT immunoreactive cells (IR), detected throughout the GIT of three bats, were the most predominant gastrointestinal endocrine cells. GAS-IR cells in A. geoffroyi were found at the base of the pyloric gland, while in G. soricina they could also be observed in the middle to basal portions of the gland. GLUC-IR cells were located in the fundic region of A. geoffroyi, G. soricina and D. rotundus. These endocrine cells were more abundant in the sanguivorous bat. In nectarivorous bats were compared to sanguivorous bat, which differ in dietary habits, difference in the distribution and relative frequency of gut endocrine cells would be predicted. The absence of some, and decrease in frequency of other, gastrointestinal endocrine cells may reflect, in part, its interspecies differences or dietary habits.

A comparative immunohistochemical study of endocrine cells in the digestive tract of two frugivorous bats: Artibeus cinerius and Sturnira lilium

The purpose of the present study was to examine the serotonin (5-hydroxytryptamine, 5-HT), gastrin (GAS), cholecystokinin (CCK) and glucagon (GLUC) endocrine cells in the gastrointestinal tract of frugivorous Phillostomidae bats, Sturnira lilium and Artibeus cinerius, to clarify the correlation between distribution of cell types and their relative frequency, with feeding habits. Five portions of the gastrointestinal tract--fundus, pilorus, and three parts of the intestine, I, II and III--were examined. Most of the immunoreactive cells in the stomach and intestine were of triangular, oval or piriform shape. Serotonin-immunoreactive cells were most commonly found in the S. lilium intestine I (66.6+/-9.9) and the A. cinerius intestine III (35+/-18). Gastrin-immunoreactive cells were the most abundant cell type in the pyloric glands of both species. They were more numerous in A. cinerius (126.9+/-27.4) than in S. lilium (75.8+/-1.8). CCK-immunoreactive cells were found in the alimentary tract epithelia at moderate frequencies in both species. GLUC-immunoreactive cells were detected at very low or low frequencies. This study suggests that there is a correlation between endocrine cell distribution and frequency, and the feeding habits of the bats.