In vivo positron emission tomography imaging of decreased parasympathetic innervation in the gut of vagotomized patients.

BACKGROUND: Parasympathetic neuropathy is a key feature in many common disorders, including diabetes, neurological disorders, and cancers, but few objective methods exist for assessing damage to the parasympathetic nervous system, particularly in the gastrointestinal system. This study aimed to validate the use of 11 C-donepezil positron emission tomography (PET) to assess parasympathetic integrity in a group of vagotomized patients. METHODS: Sixteen healthy controls and 12 patients, vagotomized due to esophagectomy, underwent 11 C-donepezil PET, measurement of colonic transit time, quantification of plasma pancreatic polypeptide (PP), and assessment of subjective long-term symptoms. KEY RESULTS: Vagotomized patients had significantly decreased PET signal in the small intestine and colon compared with healthy controls (5.7 [4.4-7.9] vs 7.4 [4.5-11.3], P = .01 and 1.4 [1.1-2.1] vs 1.6 [1.4-2.4], P < .01, respectively). Vagotomized patients also displayed a significantly increased colonic transit time (2.9 ± 0.9 h vs 1.9 ± 0.8 h), P < .01 and increased volumes of the small intestine and colon (715 ccm [544-1177] vs 443 ccm [307-613], P < .01 and 971 ccm [713-1389] vs 711 ccm [486-1394], P = .01, respectively). Patients and controls did not differ in PP ratio levels after sham feeding, but PP ratio at 10 minutes. after sham feeding and PET signal intensity in the small intestine was positively correlated (P = .03). CONCLUSIONS AND INFERENCES: We found significantly decreased 11 C-donepezil signal in the intestine of vagotomized patients, supporting that 11 C-donepezil PET is a valid measure of intestinal parasympathetic denervation.

Pancreatic Polypeptide-Secreting Tumour of the Proximal Pancreas (PPoma)-Ultra Rare Pancreatic Tumour: Clinically Malign, Histologically Benign.

Background and objectives: Here we report a rare case of a pancreatic polypeptide-secreting tumour (PPoma) discovered by accident during an autopsy. These PPomas occur in less than 2% of all pancreatic neoplasms and are almost exclusively silent, i.e., they are non-functional. Symptoms arising from PPoma are due to its compression of surrounding tissue. Materials and methods: The autopsy was performed on a 68-year-old male diagnosed with multiple endocrine neoplasm type 1 (MEN1) due to the patient's sudden death. Results: A solitary, densely fibrotic, pink-brown tumour, 18 mm in size tumorous mass, was localised in the head of the pancreas. Microscopically, the tumour had a glandular structure with a tubuloacinar arrangement of the cells. Immunohistochemically, we detected strong PP (pancreatic polypeptide) intracytoplasmic activity and negative glucagon activity. The PPoma was located in the head of the pancreas, likely resulting in the obstruction of the main pancreatic and common bile duct. Conclusions: To the best of our knowledge, this is the first report suggesting the association of PPomas with MEN1. Also, the PPoma could be the cause of acute hemorrhagic pancreatitis due to its location.

Low subjective socioeconomic status stimulates orexigenic hormone ghrelin - A randomised trial.

Recent evidence suggests that lower perceived socioeconomic status is linked to increased appetite and intake of greater calories. Yet, whether insecurity of socioeconomic resources directly influences regulatory systems of appetite and energy intake is not known. Considering psychological states, mindsets and beliefs have shown to meaningfully affect physiological responses to food, the present study tested the hypothesis that low subjective socioeconomic status (SSS) will have a direct influence on physiological responses, such as appetite-related hormones (ghrelin, pancreatic polypeptide and insulin). Forty-eight healthy males were randomly (crossover, counterbalanced) assigned, to two experimental conditions where participants were either experimentally induced to feel low SSS or not (control; CON). Feelings of low SSS resulted in an increase in active ghrelin (an orexigenic hormone) following the SSS manipulation compared with baseline, while no change in active ghrelin was observed in CON. Furthermore, participants reported lower fullness and satiety following low SSS compared with CON. Our findings demonstrate that SSS may influence hunger regulation and appetite, and suggest that physiological systems regulating energy balance (i.e. caloric resources) may also be sensitive to perceived deprivation or imbalances in critical non-food resources (socioeconomic resources).

Modified Western blotting for insulin and other diabetes-associated peptide hormones.

Now, the quantification of proinsulin/insulin contents within organisms tends to be evaluated only by enzyme-linked immunosorbent assay (ELISA), although assessing the adequacy of results by some quantification method is important. Remarkably, few scientific papers use detection by Western blotting (WB), another immunological assay, of proinsulin/insulin. We found two problems with quantification of insulin and proinsulin by general WB: the shape of an insulin band in gel electrophoresis is distorted, and the retention potency to a blotting membrane of the peptide hormones (mainly insulin) is low. We solved the first problem by optimizing the sodium dodecyl sulfate concentration in the sample buffer and the second problem by glutaraldehyde fixation following treatment with a blocking solution for a short time. The improvements were confirmed by quantification of proinsulin/insulin in standards, MIN6c4 cell lysates, and MIN6c4 culture supernatants. Furthermore, we showed that the modified WB is applicable to other diabetes-associated peptide hormones: insulin analogs, glucagon, GLP-1s, somatostatins, ghrelins, and pancreatic polypeptide. Our data showed that the modified WB can contribute to qualitative or quantitative analyses of diabetes-associated peptides by providing analytical information based on electrophoresis, although ELISA, which is an almost exclusive method in the quantification of peptide hormones, supplies only numerical data.

Abnormalities in ileal stem, neurogenin 3, and enteroendocrine cells in patients with irritable bowel syndrome.

BACKGROUND: This study examined whether the densities of stem- and enteroendocrine cell progenitors are abnormal in the ileum of patients with irritable bowel syndrome (IBS), and whether any abnormalities in ileal enteroendocrine cells are correlated with abnormalities in stem cells and enteroendocrine cell progenitors. METHODS: One hundred and one IBS patients covering all IBS subtypes were recruited, and 39 non-IBS subjects were included as a control group. The patients and controls underwent standard colonoscopies, during which biopsy specimens were obtained from the ileum. The biopsy specimens were stained with hematoxylin-eosin and immunostained for Musashi-1 (Msi-1), neurogenin 3 (NEUROG3), chromogranin A (CgA), serotonin, peptide YY (PYY), oxyntomodulin (enteroglucagon), pancreatic polypeptide, and somatostatin. The immunoreactive cells were quantified by computerized image analysis. RESULTS: The densities of Msi-1, NEUROG3, CgA, and serotonin cells were reduced in all IBS patients and in patients with diarrhea-predominant IBS (IBS-D), mixed-diarrhea-and-constipation IBS (IBS-M), and constipation-predominant (IBS-C) relative to the control subjects. While the PYY cell density was increased in IBS-C relative to controls, it did not differ between control subjects and IBS-D and IBS-M patients. The densities of Msi-1 and NEUROG3 cells were strongly correlated with that of CgA cells. CONCLUSIONS: The abnormalities in the ileal enteroendocrine cells appear to be caused by two mechanisms: (1) decreases in the clonogenic activity of the stem cells and in the endocrine-cell progenitors differentiating into enteroendocrine cells, and (2) switching on the expression of PYY and switching off the expression of certain other hormones in other types of the enteroendocrine cells.

Enteroendocrine, Musashi 1 and neurogenin 3 cells in the large intestine of Thai and Norwegian patients with irritable bowel syndrome.

OBJECTIVES: The prevalence, gender distribution and clinical presentation of IBS differ between Asian and Western countries. This study aimed at studying and comparing enteroendocrine, Musashi 1 (Msi 1) and neurogenin 3 (neurog 3) cells in Thai and Norwegian IBS patients. MATERIAL AND METHODS: Thirty Thai and 61 Norwegian IBS patients as well as 20 Thai and 24 Norwegian controls were included. Biopsy samples were taken from each of the sigmoid colon and the rectum during a standard colonoscopy. The samples were immunostained for serotonin, peptide YY, oxyntomodulin, pancreatic polypeptide, somatostatin, Msi 1 and neurog 3. The densities of immunoreactive cells were determined with computerized image analysis. RESULTS: The densities of several enteroendocrine cell types were altered in both the colon and rectum of both Thai and Norwegian IBS patients. Some of these changes were similar in Thai and Norwegian IBS patients, while others differed. CONCLUSIONS: The findings of abnormal densities of the enteroendocrine cells in Thai patients support the notion that enteroendocrine cells are involved in the pathophysiology of IBS. The present observations highlight that IBS differs in Asian and Western countries, and show that the changes in large-intestine enteroendocrine cells in Thai and Norwegian IBS patients might be caused by different mechanisms.

Immunohistochemical distribution of neuropeptide Y, peptide YY, pancreatic polypeptide-like immunoreactivity and their receptors in the epidermal skin of healthy women.

Few studies have suggested that neuropeptide Y (NPY) could play an important role in skin functions. However, the expression of NPY, the related peptides, peptide YY (PYY) and pancreatic polypeptide (PP) and their receptors have not been investigated in human skin. Using specific antisera directed against NPY, PYY, PP and the Y1, Y2, Y4 and Y5 receptor subtypes, we investigated here the expression of these markers. NPY-like immunoreactivity (ir) in the epidermal skin could not be detected. For the first time we report the presence of positive PP-like ir immunofluorescent signals in epidermal cells, i.e. keratinocytes of skin from three areas (abdomen, breast and face) obtained as surgical left-overs. The immunofluorescent signal of PP-like ir varies from very low to high level in all three areas. In contrast, PYY-like ir is only expressed in some cells and with varied level of intensity. Furthermore and for the first time we observed specific Y1 and Y4 receptor-like ir in all epidermal layers, while the Y2 and Y5 subtypes were absent. Interestingly, as seen in human epidermis, in Episkin, a reconstituted human epidermal layer, we detected the presence of PP-like as well as Y1-like and Y4-like ir. These data have shown the presence and distribution of PYY, PP and Y1 and Y4 receptors in the human skin and Episkin, suggesting possible novel roles of NPY related peptides and their receptors in skin homeostasis.

[Amylin under examination. Fibrillation - cytotoxic pancreatic polypeptide aggregation]. / Amylina w badaniach eksperymentalnych.Fibrylacja ­ cytotoksyczna agregacja polipeptydutrzustki.

In patients or animals affected by type 2 diabetes mellitus (DM2, non-insulin dependent diabetes mellitus [NIDDM]), some pathological deposits, called amyloid, are observed among cells of islets of Langerhans. Among other constituents, the deposits consist of an insoluble, fibrillar form of polypeptide neurohormone called amylin, produced by pancreatic beta cells. It is thought that formation of fibrillar deposits of misfolded and aggregated polypeptide is highly toxic to beta cells and leads to cell dysfunction, cell loss, pancreas destruction and progress of the disease. Due to the extreme insolubility of this polypeptide and its instant fibrillation, amylin constitutes a methodological problem, and there is a need for a special methodology in experiments. Some mechanisms and factors that govern amylin fibrillization are rather poorly understood. This article presents amylin as a fibrillating molecule and some methods and methodological aspects and problems that emerge at successive steps during the fibrillation process, including hypothesized cytotoxicity mechanisms of this polypeptide.

Distribution of islet hormones in human adult pancreatic ducts.

BACKGROUND/AIMS: The source of insulin-secreting cells from adult duct system is attractive, but its clinical practice remains poorly understood. Here, we aimed at identifying the distribution of secreted hormone reactive cells in adult ducts. METHODS: Consecutive pancreatic slices from nondiabetic subjects were subjected to immunohistochemistry and immunofluorescence to screen islet hormones (insulin; glucagon, Glu; somatostatin, Som; pancreatic polypeptide, PP) and exocrine biomarkers (cytokeratin 19, CK19; chromogranin A, CgA; amylase). All pancreatic sections were imaged using an optical or confocal microscope. RESULTS: Immunostaining results showed that insulin was expressed in adult ducts, in which the cell count was more than other islet hormone immunoactive cells. CK19-positive cells are mainly distributed in the ducts, whereas CgA-labeled cells are localized in endocrine cells. The duct branches visibly exhibited cell populations that co-expressed islet hormones in exocrine cell populations. CONCLUSIONS: In this report, our findings demonstrate that adult ductal cells that produce insulin may contribute to beta-cell proliferation.

Endocrine cells in the ileum of patients with irritable bowel syndrome.

AIM: To study the ileal endocrine cell types in irritable bowel syndrome (IBS) patients. METHODS: Ninety-eight patients with IBS (77 females and 21 males; mean age 35 years, range 18-66 years) were included, of which 35 patients had diarrhea (IBS-D), 31 patients had a mixture of both diarrhea and constipation (IBS-M), and 32 patients had constipation (IBS-C) as the predominant symptoms. The controls were 38 subjects (26 females and 12 males; mean age 40 years, range 18-65 years) who had submitted to colonoscopy for the following reasons: gastrointestinal bleeding, where the source of bleeding was identified as hemorrhoids (n = 24) or angiodysplasia (n = 3), and health worries resulting from a relative being diagnosed with colon carcinoma (n = 11). The patients were asked to complete the: Birmingham IBS symptom questionnaire. Ileal biopsy specimens from all subjects were immunostained using the avidin-biotin-complex method for serotonin, peptide YY (PYY), pancreatic polypeptide (PP), enteroglucagon, and somatostatin cells. The cell densities were quantified by computerized image analysis, using Olympus cellSens imaging software. RESULTS: The gender and age distributions did not differ significantly between the patients and the controls (P = 0.27 and P = 0.18, respectively). The total score of Birmingham IBS symptom questionnaire was 21 ± 0.8, and the three underlying dimensions: pain, diarrhea, and constipation were 7.2 ± 0.4, 6.6 ± 0.4, and 7.2 ± 0.4, respectively. The density of serotonin cells in the ileum was 40.6 ± 3.6 cells/mm² in the controls, and 11.5 ± 1.2, 10.7 ± 5.6, 10.0 ± 1.9, and 13.9 ± 1.4 cells/mm² in the all IBS patients (IBS-total), IBS-D, IBS-M, and IBS-C patients, respectively. The density in the controls differed significantly from those in the IBS-total, IBS-D, IBS-M, and IBS-C groups (P < 0.0001, P = 0.0001, P = 0.0001, and P < 0.0001, respectively). There was a significant inverse correlation between the serotonin cell density and the pain dimension of Birmingham IBS symptom questionnaire (r = -0.6, P = 0.0002). The density of PYY cells was 26.7 ± 1.6 cells/mm(2) in the controls, and 33.1 ± 1.4, 27.5 ± 1.4, 34.1 ± 2.5, and 41.7 ± 3.1 cells/mm² in the IBS-total, IBS-D, IBS-M, and IBS-C patients, respectively. This density differed significantly between patients with IBS-total and IBS-C and the controls (P = 0.03 and < 0.0001, respectively), but not between controls and, IBS-D, and IBS-M patients (P = 0.8, and P = 0.1, respectively). The density of PYY cells correlated significantly with the degree of constipation as recorded by the Birmingham IBS symptom questionnaire (r = 0.6, P = 0.0002). There were few PP-, enteroglucagon-, and somatostatin-immunoreactive cells in the biopsy material examined, which made it impossible to reliably quantify these cells. CONCLUSION: The decrease of ileal serotonin cells is associated with the visceral hypersensitivity seen in all IBS subtypes. The increased density of PYY cells in IBS-C might contribute to the constipation experienced by these patients.

Global chain properties of an all l-α-eicosapeptide with a secondary α-helix and its all retro d-inverso-α-eicosapeptide estimated through the modeling of their CZE-determined electrophoretic mobilities.

Several global chain properties of relatively long peptides composed of 20 amino acid residues are estimated through the modeling of their experimental effective electrophoretic mobilities determined by CZE for 2 < pH < 6. In this regard, an all l-α-eicosapeptide, including a secondary α-helix (Peptide 1) and its all retro d-inverso-α-eicosapeptide (Peptide 2), are considered. Despite Peptides 1 and 2 are isomeric chains, they do not present similar global conformations in the whole range of pH studied. These peptides may also differ in the quality of BGE components chain interactions depending on the pH value. Three Peptide 1 fragments (Peptides 3, 4, and 5) are also analyzed in this framework with the following purposes: (i) visualization of the effects of initial and final strands at each side of the α-helix on the global chain conformations of Peptide 1 at different pHs and (ii) analysis of global chain conformations of Peptides 1 and 2, and Peptide 1 fragments in relation to their pI values. Also, the peptide maximum and minimum hydrations predicted by the model, compatible with experimental effective electrophoretic mobilities at different pHs, are quantified and discussed, and needs for further research concerning chain hydration are proposed. It is shown that CZE is a useful analytical tool for peptidomimetic designs and purposes.

Immunohistochemical localization of somatostatin and pancreatic polypeptide in smokers with chronic pancreatitis.

Recent studies have demonstrated a significant role of tobacco smoking in the development of chronic pancreatitis. Although there are published papers on the effects of cigarette smoking on insulin secretion in patients, no data are available on the effects of smoking on pancreatic endocrine cells secreting somatostatin and pancreatic polypeptide. The aim of the study was to evaluate the effects of cigarette smoking on endocrine pancreatic function by immunolocalization of somatostatin and pancreatic polypeptide in the pancreas from smokers and non-smoking patients with chronic pancreatitis in comparison with healthy controls. The LSAB2-HRP technique with polyclonal antibodies was used for the immunolocalization of somatostatin and pancreatic polypeptide in histological preparations of the pancreas. The intensity of immunohistochemical reaction was calculated with digital image analysis. The study demonstrated increased numbers of somatostatin (D) secreting cells and pancreatic polypeptide (PP) cells and their altered location in pancreatic islets and parenchyma of smoking patients with chronic pancreatitis, as compared to non-smoking patients and healthy controls. Smoking patients showed significantly higher immunostaining of the hormones in the pancreas compared to non-smoking patients and healthy persons. This study indicates that smoking may play a significant role in the development of endocrine disturbances in the development of chronic pancreatitis.

Biochemical markers for gastroenteropancreatic neuroendocrine tumours (GEP-NETs).

Biochemical markers are applied in gastroenteropancreatic neuroendocrine tumours (GEP-NETs) for diagnostic, prognostic or predictive purposes. Chromogranin A is the most important general marker and it is recommended to be measured in every patient with a suspected NET, whereas Neuron Specific Enolase is elevated mainly in poorly differentiated NETs. Pancreatic Polypeptide is used in the diagnosis of pancreatic non-functioning NETs, whereas Chorionic Gonadotrophin has an adjunctive role. In the case of functioning tumours, specific markers should be sought and monitored during follow up. Endogenous hyperinsulinemia is suggested in the presence of non-suppressible insulin and proinsulin levels during hypoglycemia, whereas high fasting or stimulated gastrin levels along with elevated gastric acid output are diagnostic for the Zollinger-Ellison syndrome. Glucagon, vasoactive intestinal polypeptide (VIP) and somatostatin are markers for glucagonoma, VIP-oma and somatostatinoma syndromes respectively. In case of ectopic paraneoplastic syndrome, the relevant hormone serves as a diagnostic and prognostic marker.

Computer-assisted three-dimensional reconstruction of the fetal pancreas including the supplying arteries according to immunohistochemistry of pancreatic polypeptide.

PURPOSE: Computer-assisted three-dimensional reconstruction of the fetal human pancreas was prepared to reconsider topographical relation between the dorsal/ventral anlagen and the vascular supply. METHODS: Tissue sections from the upper abdominal viscera of three fetuses were examined. Sections were immunohistochemically stained to determine pancreatic polypeptide expression, a marker of the ventral pancreas. RESULTS: The immunohistochemical findings were used to create three-dimensional computer-assisted reconstructions to identify pancreatic arteries. The narrowest part of the pancreas, or the neck, corresponding to a part of the dorsal pancreas, was located on the left side of the common bile duct, portal vein and gastroduodenal artery (GDA). The posterior arterial arcade accompanied the ventral pancreas, whereas the anterior arcade did not. In contrast to the GDA, the splenic artery was clearly separated from the neck in fetuses. The GDA appears to be the primary and stable arterial supply for the neck of the pancreas. CONCLUSIONS: This observation may have implications for the preservation of the neck with the GDA during pancreaticoduodenectomy for benign and low-grade malignant diseases.

Proteomic analysis of polypeptides captured from blood during extracorporeal albumin dialysis in patients with cholestasis and resistant pruritus.

Albumin dialysis using the molecular adsorbent recirculating system (MARS) is a new therapeutic approach for liver diseases. To gain insight into the mechanisms involved in albumin dialysis, we analyzed the peptides and proteins absorbed into the MARS strong anion exchange (SAX) cartridges as a result of the treatment of patients with cholestasis and resistant pruritus. Proteins extracted from the SAX MARS cartridges after patient treatment were digested with two enzymes. The resulting peptides were analyzed by multidimensional liquid chromatography coupled to tandem mass spectrometry. We identified over 1,500 peptide sequences corresponding to 144 proteins. In addition to the proteins that are present in control albumin-derived samples, this collection includes 60 proteins that were specific to samples obtained after patient treatment. Five of these proteins (neutrophil defensin 1 [HNP-1], secreted Ly-6/uPAR-related protein 1 [SLURP1], serum amyloid A, fibrinogen alpha chain and pancreatic prohormone) were confirmed to be removed by the dialysis procedure using targeted selected-reaction monitoring MS/MS. Furthermore, capture of HNP-1 and SLURP1 was also validated by Western blot. Interestingly, further analyses of SLURP1 in serum indicated that this protein was 3-fold higher in cholestatic patients than in controls. Proteins captured by MARS share certain structural and biological characteristics, and some of them have important biological functions. Therefore, their removal could be related either to therapeutic or possible adverse effects associated with albumin dialysis.

Regional distribution and relative frequency of gastrointestinal endocrine cells in the ddN mice: an immunohistochemical study.

The distributions and frequencies of some endocrine cells in the eight portions of the gastrointestinal (GI) tract - fundus, pylorus, duodenum, jejunum, ileum, cecum, colon and rectum of the ddN mouse, were studied with immunohistochemical method using seven types of antisera against chromogranin (Cg) A serotonin, somatostatin, glucagon, gastrin, cholecystokinin (CCK)-8 and human pancreatic polypeptide (hPP). In the GI tract of ddN mice, CgA, serotonin, somatostatin, glucagon, gastrin, CCK-8 immunoreactive (IR) cells were identified with various frequencies, but hPP-IR cells were not observed in this study. Most of IR cells in the intestinal portion were generally spherical or spindle in shape (open type cell) whereas cells showing round in shape (close type cell) were found in the intestinal gland and stomach regions occasionally. They showed the highest frequency in the pylorus or colon. CgA-IR cells were observed from the pylorus to ileum. Serotonin-IR cells were detected throughout the whole GI tract except for the fundus. Somatostatin-IR cells were demonstrated throughout the whole GI tract except for the cecum and colon. Gastrin and CCK-8-IR cells were restricted to the pylorus and duodenum. In addition, a few glucagon-IR cells were restricted to the fundus and rectum. In conclusion, the general distribution patterns and relative frequency of GI endocrine cells of the ddN mouse was similar to that of other strains of mice. However, some strain and/or species-dependent unique distributions and frequencies of endocrine cells were also observed in the present study.

Las hormonas gastrointestinales en el control de la ingesta de alimentos / Gastrointestinal hormones in food intake control

El descubrimiento de la existencia de hormonas gastrointestinales que modulan la homeostasis energética ha despertado un gran interés. Algunas de estas hormonas, actuando en el hipotálamo o el núcleo del tracto solitario en el tronco encefálico, ejercen efectos moduladores del apetito y la saciedad. En términos generales, las señales endocrinas generadas en el tracto gastrointestinal tienen efecto anorexigénico directo o indirecto a través del sistema nervioso vegetativo. Sólo la ghrelina, hormona producida en el estómago, se ha asociado de manera consistente con el inicio de la ingesta y se la considera una de las principales señales orexigénicas en los modelos animales estudiados y en humanos. En esta revisión, se describen brevemente las principales hormonas de origen gastrointestinal implicadas en la regulación del apetito. Dada la importancia que los trastornos de la ingesta de alimentos, especialmente la obesidad, han adquirido, un mejor conocimiento de los mecanismos de acción de estas señales endocrinas podría contribuir al desarrollo de nuevas moléculas que incrementen y mejoren nuestro arsenal terapéutico para tratar la obesidad y las enfermedades crónicas relacionadas con ella (AU)

The discovery of gut hormones regulating the energy balance has aroused great interest in the scientific community. Some of these hormones modulate appetite and satiety, acting on the hypothalamus or the solitary tract nucleus in the brainstem. In general, the endocrine signals generated in the gut have direct or indirect (through the autonomous nervous system) anorexigenic effects. Only ghrelin, a gastric hormone, has been consistently associated with the initiation of food intake and is regarded as the main orexigenic signal both in animal models and humans. In this review, we provide a brief description of the major gastrointestinal hormones implicated in the regulation of food intake. Given the increased importance of food intake disturbances, especially obesity, a better understanding of the underlying mechanisms of action of the gastrointestinal hormones might contribute to the development of new molecules that could increase the therapeutic arsenal for treating obesity and its associated comorbidities (AU)

Immunohistochemical staining of human islet cells with region-specific antibodies against secretogranins II and III.

Chromogranins and secretogranins belong to the granin family of proteins, which are expressed in neuroendocrine and nervous tissue. In earlier publications we have described the development of region-specific antibodies against CgA and CgB. In this study we describe antibodies to SgII and SgIII and their usefulness for immunohistochemical staining. Peptides homologous to defined parts of secretogranins II and III were selected and synthesized. Antibodies were raised and immunostainings were performed on normal human pancreas. The SgII 154-165 (N-terminal secretoneurin), SgII 172-186 (C-terminal secretoneurin) and SgIII antibodies immunostained all insulin-immunoreactive cells, most of the glucagon cells and some of the pancreatic polypeptide cells. The SgII 225-242 antibody immunostained only the insulin-containing cells. None of the antibodies immunostained the somatostatin cells. This study is the first observation of the expression of SgIII in human tissues, where we show expression of SgIII in three of the four major islet cell types in human pancreas.