Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vasoactive intestinal peptide (VIP) is a neuropeptide with a broad range of biological activities in various tissues. After interaction with its membrane receptor, VIP generally induces a very large increase in the intracellular cyclic AMP level. Receptors for VIP have been described in numerous tissues and cell lines. The first results on VIP receptor structure have been obtained by covalent cross-linking using bifunctional reagents. The molecular mass of the different components characterized in this way differs greatly according to the species and the tissue used. This heterogeneity may reflect either a difference in the length of the cross-linked polypeptide backbone or differently glycosylated forms of the same polypeptide. The VIP binding site of intact human adenocarcinoma cells (HT29 cells) is an Mr 64,000 glycoprotein with 20kDa of N-linked oligosaccharide side chains containing sialic acid. The structure of the VIP binding site from HT29 cell is compared, first to the structure of the VIP receptor from other tissues, particularly that from rat liver, and second to the structure of the hepatic glucagon binding site. Recently, solubilization of the VIP receptor in an active form has provided a new way of studying this receptor. The HT29 cell line is an appropriate model to study the dynamics of the VIP receptor. After binding to its receptor, VIP is rapidly internalized, probably by receptor-mediated endocytosis. This internalization leads to a decrease in the cell surface receptor number and simultaneously to a homologous desensitization of adenylate cyclase. VIP is then degraded in the lysosomes, while most of the receptors are recycled back to the cell surface. The presence of an intracellular pool of unoccupied VIP receptors has been demonstrated after inactivation of the cell surface receptors by chymotrypsin. The kinetics of the receptor reappearance at the cell surface, after inactivation by chymotrypsin or after receptor-mediated endocytosis, indicate 2 possible intracellular pathways for occupied and unoccupied VIP receptors.
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PMID:The vasoactive intestinal peptide (VIP) receptor: recent data and hypothesis. 285 63

A nine-year-old mixed breed dog was presented with a history of mild generalized seizures, weakness, and muscle fasciculations, following periods of excitement and exercise. Investigative procedures included haematology, chemical pathology, faecal analysis, urinalysis, cerebrospinal fluid analysis, hormone assays, computerized axial tomography and scintigraphic imaging. Results of these investigations revealed hypoglycaemia (blood glucose 1.9 mmol l-1, hyperinsulinism (111 muu ml-1) and an amended insulin-glucose ratio of 2643. The glucagon tolerance test was typical for an insulin producing pancreatic islet cell tumour and pancreas scintigraphic imaging revealed focal lesions in the pancreas and liver. Seizures were initially controlled by dietary means and by limiting exercise. Eventual control was obtained by treatment with prednisolone (1 mg kg-1 on alternate days) and diazoxide (10 mg kg-1 in divided doses daily). Post mortem examination confirmed the presence of a pancreatic islet cell adenocarcinoma with hepatic metastasis.
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PMID:An insulinoma causing hypoglycaemia and seizures in a dog: case report and literature review. 285 64

A case of prostatic carcinoma with the cellular patterns of an adenocarcinoma and carcinoid tumor is reported. The tumor contained ultrastructural dense core neuroendocrine granules, and immunoperoxidase staining revealed prostatic acid phosphatase, prostatic-specific antigen, chromogranin, neuron-specific enolase, serotonin, adrenocorticotrophic hormone (ACTH), somatostatin, parathormone, calcitonin, bombesin, and glucagon but no insulin. The patient had exhibited hypercalcemia that may have been related to hormone production by the tumor. The literature on the endocrine aspect of the prostate and its tumor is reviewed.
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PMID:Prostatic carcinoma with endocrine features. A report of a neoplasm containing multiple immunoreactive hormonal substances. 289 Dec 93

[125I]Monoiodinated vasoactive intestinal peptide (125I-VIP) was cross-linked with human colonic adenocarcinoma cells (HT29 cells) grown as a monolayer using dithiobis(succinimidylpropionate) as cross-linking reagent. The cross-linked polypeptides were separated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. A major polypeptide of Mr = 67 000 was characterized and it behaved like a high-affinity binding site for VIP according to the following data. The concentration of native VIP (0.5 nM) giving half-maximum inhibition of 125I-VIP covalent cross-linking with this polypeptide was very similar to that giving half-maximum displacement of 125I-VIP on HT 29 cells (0.6 nM). Glucagon or insulin was unable to inhibit the labelling of the Mr-67 000 component. In our experimental conditions neither specific 125I-VIP binding nor covalent labelling was observed with monolayers of Madin Darby canine kidney epithelial cells (MDCK cells) or African green monkey kidney fibroblasts (Vero cells) while the Mr-67 000 polypeptide was also characterized with human rectal adenocarcinoma cells (HRT 18 cells), known to possess the VIP receptor. Preincubation of HT 29 cells with native VIP at 37 degrees C, before 125I-VIP binding and subsequent cross-linking reaction, decreased the labelling of the Mr-67 000 polypeptide up to 80%. Assuming one molecule of 125I-VIP cross-linked per polypeptide, we have characterized, for the first time, a major polypeptide of Mr = 64 000, which belongs to the high-affinity VIP binding site of an intestinal human cell line.
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PMID:Covalent cross-linking of vasoactive intestinal peptide (VIP) to its receptor in intact colonic adenocarcinoma cells in culture (HT 29). 299 66

The human colon adenocarcinoma cell line HT-29 in culture exhibits a cyclic AMP production system highly sensitive to vasoactive intestinal peptide (VIP), making HT-29 cells a unique cultured cell system for studying the mechanism of VIP action [Laburthe, Rousset, Boissard, Chevalier, Zweibaum & Rosselin (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 2772-2775]. The quantitative characteristics of VIP receptors in HT-29 cells and their structural requirement and molecular size were studied. 125I-labeled VIP bound in a time-dependent manner to HT-29 cell homogenates. At equilibrium (60 min incubation at 30 degrees C), unlabelled VIP in the 0.01-10 nM concentration range competed with 125I-VIP for binding to cell homogenates. Scatchard analysis of binding data gave a straight line, indicating that VIP bound to a single population of sites with a KD of 0.12 +/- 0.02 nM and a capacity of 120 +/- 9 fmol/mg of protein. The structural requirement of these receptors was studied with peptides structurally related to VIP, either natural or synthetic. Several peptides inhibited 125I-VIP binding to HT-29 cell homogenates with the following order of potency, which is typical of the human VIP receptor: VIP (IC50 = 0.1 nM) greater than VIP-(2-28)-peptide (IC50 = 13 nM) greater than human growth hormone releasing factor (IC50 = 56 nM) greater than peptide histidine isoleucine amide (IC50 = 80 nM) greater than secretin (IC50 greater than 10 000 nM). To characterize the molecular component(s) of the VIP receptor in HT-29 cells, 125I-VIP was covalently bound to cell homogenates by using the cross-linker dithiobis(succinimidyl propionate). Sodium dodecyl sulphate/polyacrylamide-gel autoradiographic studies of affinity-labelled cell homogenates revealed two major bands, corresponding to 125I-VIP-protein complexes of Mr 66 000 and 16 000. The labelling of the Mr-66 000 component was specific, since it was abolished by native VIP, whereas that of the Mr-16 000 component was not. Densitometric scanning of autoradiographs indicated that the labelling of the Mr-66 000 complex was inhibited by low VIP concentrations in the 0.1-10 nM range (IC50 = 0.6 nM), but was unaffected by 1 microM-glucagon or octapeptide of cholecystokinin. It was also decreased by VIP-(2-28)-peptide with a potency 1% that of VIP. Assuming that one molecule of 125I-VIP bound per molecule of protein, one protein of Mr 63 000 was identified as a component of the VIP receptor in HT-29 cells.
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PMID:Molecular identification and structural requirement of vasoactive intestinal peptide (VIP) receptors in the human colon adenocarcinoma cell line, HT-29. 299 37

The prevalence of endocrine differentiation of conventional gastric adenocarcinoma was evaluated on the 212 cases (including 62 mucosal carcinomas) of consecutively resected stomach for adenocarcinoma in our hospital using anti-chromogranin A (CGA) antibodies. CGA-positive cells were found in 28 of 150 cases (18.7%) as an integral tumor component. In immunocytochemistry and electron microscopic examinations, we could classify these 28 cases into three groups according to the distribution patterns of CGA-positive cells. The first group consisted of 12 cases in which scattered CGA-positive cells were located in neoplastic glands. The second group consisted of six cases of scirrhous carcinoma in which CGA-positive cells were separated by fibrovascular tissue. The third group consisted of ten cases in which the positive cells were present in clusters. No definite correlation was recognized between the appearance of CGA cells and histologic types of predominance. In the analysis of the hormonal substances coexpressed by CGA-positive cells, immunoreactive serotonin (SER) was found most frequently, and somatostatin (SS), gastrin (GAS), glucagon/glicentin (GLU/GLI), and peptide-tyrosine-tyrosine (PYY) like immunoreactivities were found in a few tumor cells. CGA-positive cells occupied limited parts of the tumors in most cases, and they were noticeably more frequent in advanced stage cases. This might explain why endocrine differentiation reflects the dysexpression of the neoplastic stem cells. Furthermore, absence of mitotic figures in this type of cell and negativity of a single colony composed exclusively of CGA cells in metastatic foci suggested that these cells are in a dormant phase and are probably postmitotic.
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PMID:Endocrine differentiation of gastric adenocarcinoma. The prevalence as evaluated by immunoreactive chromogranin A and its biologic significance. 304 73

We present the first reported case (to our knowledge) of duodenal gangliocytic paraganglioma (GPG) to be associated with an underlying invasive adenocarcinoma. The patient, a 71-year-old man, presented with epigastric tenderness and was found to have metastatic adenocarcinoma in two regional lymph nodes. Immunohistochemical evaluation of the GPG demonstrated positive staining for gastrin, glial-fibrillary acidic protein, glucagon, neuron-specific enolase, pancreatic polypeptide, S100 protein, somatostatin, and substance P. The clinical, pathologic, and immunohistochemical features of GPG are discussed, with a review of the literature.
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PMID:Gangliocytic paraganglioma associated with duodenal adenocarcinoma. Case report with immunohistochemical evaluation. 380 Jun 4

A morphologic, histochemical, and immunocytochemical study of 20 cases of pure gastrointestinal carcinoids, adenocarcinomas, and mixed neoplasms composed of both elements, so-called composite carcinoma-carcinoid tumors (CCC), was undertaken in order to correlate the morphologic patterns with the immunocytochemical localization of carcinoembryonic antigen (CEA), serotonin, and a battery of polypeptide hormones (calcitonin, glucagon, insulin, gastrin, somatostatin, and adrenocorticotropin [ACTH]). Paraffin sections from five pure carcinoids, seven pure adenocarcinomas, and eight CCC from the stomach, small bowel, appendix, and colon were studied with mucicarmine, silver impregnation stains, and a peroxidase-anti-peroxidase technic. Of the eight CCC, all were mucin positive, four were argyrophilic, and three were argentaffin positive. CEA was present in all eight, serotonin in seven, and calcitonin in one. No other neurohormonal peptides were demonstrated. The distribution of serotonin and CEA generally corresponded to the morphologic pattern, but discordance was observed in two cases, i.e., serotonin was not always localized to areas of carcinoid and CEA not always confined to areas of carcinoma. All five pure carcinoids demonstrated intracytoplasmic localization of serotonin, whereas none contained intracytoplasmic CEA. In two cases, CEA was present within acinar lumens only. The seven colonic adenocarcinomas were argyrophil and argentaffin negative. All contained CEA within the cytoplasm and in gland lumens. None contained serotonin. None of the neurohormonal peptides was localized in either pure adenocarcinomas or carcinoids. This study reveals that among gastrointestinal neoplasms displaying morphologic patterns of adenocarcinoma and carcinoid, immunocytochemical localization of CEA and serotonin confirms their bidirectional differentiation and justifies the designation "composite carcinoma-carcinoid."
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PMID:Composite carcinoma-carcinoid tumors of the gastrointestinal tract. A morphologic, histochemical, and immunocytochemical study. 389 86

Early passage in vitro cultures of colorectal adenocarcinoma cells were used to determine if glucagon exerts a direct effect on growth of human colon cancer cells. Growth response assays indicated that glucagon generally stimulated growth between 2 and 10 micrograms/ml, with peak responses at 5 to 10 micrograms/ml. When glucagon-treated and control cultures were compared, 12 of the 14 cultures (86 percent) were stimulated by glucagon, with an increase in cells from 41 to 100 percent. The other two cultures did not respond to glucagon. These in vitro results suggest that glucagon may enhance growth of most colon cancer cells. Further studies on responsiveness to glucagon may help elucidate mechanisms of oncogenesis and suggest new therapeutic protocols for patients with colorectal cancer.
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PMID:Glucagon enhances growth of cultured human colorectal cancer cells in vitro. 407 59

A rare ovarian mixed germ cell tumor containing pancreatic tissue with islet cells was reported. The tumor, weighing 4,500 g, arose in the left ovary of a 29-year-old nulliparous unmarried woman. On section, the tumor was largely solid, but with small- to medium-sized multiple cysts which contained mucinous fluid. Microscopically, the tumor was composed predominantly of immature pancreatic tissue with islet cells budding from the glandular structures, where a few aldehyde-fuchsin-positive cells and some argyrophil cells were seen. Also, insulin-, glucagon-, or somatostatin-reactive cells were localized in these structures by immunohistochemistry. Multiple cysts were covered by a monolayer of benign-looking mucinous epithelium. The tumor contained elements of dysgerminoma, endodermal sinus tumor, immature teratoma, and mucinous adenocarcinoma as minor components. Two years after the surgery followed by chemotherapy with vincristine, actinomycin D, and cyclophosphamide, the patient became pregnant and delivered a healthy female infant.
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PMID:A rare malignant ovarian mixed germ cell tumor containing pancreatic tissue with islet cells. 609 90


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