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)

Glucagonoma is a relatively rare type of pancreatic endocrine tumor, and is often well-developed and malignant at detection. We report a case of nonfunctioning small glucagon-producing tumor that was successfully resected by laparoscopic surgery. A 63-year-old woman was admitted to our hospital for further examination of a pancreatic tumor that had been detected incidentally. Hematological data and hormone concentrations were within normal ranges. Abdominal ultrasonography and computed tomography showed a small mass in the body of the pancreas. Laparoscopic distal pancreatectomy was done. Macroscopically, the resected tumor was a yellowish-white, solid mass measuring 8 x 8 x 7 mm. The tumor cells showed positive immunohistochemical staining for chromogranin A and glucagon. The postoperative course was uneventful. To the best of our knowledge, this is the first report of laparoscopic surgery for a nonfunctioning small glucagon-producing tumor. Because of recent improvements in laparoscopic surgery technique, use of this approach for resection of pancreatic benign small endocrine tumors will likely increase in the future.
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PMID:Laparoscopic resection for nonfunctioning small glucagon-producing tumor: report of a case and review of the literature. 1459 40

Enteroendocrine cells are a complex population of intestinal epithelial cells whose hormones play critical roles in regulating gastrointestinal and whole-animal physiology. There are many subpopulations of enteroendocrine cells based on the major hormone(s) produced by individual cells. Intracellular calcium plays a critical role in regulating hormone release. Inositol 1,4,5-trisphophate (IP3) receptors regulate calcium mobilization from endoplasmic reticulum-derived calcium stores in many endocrine and excitatory cells and are expressed in the intestine. However, the specific subtypes of enteroendocrine cells that express these receptors have not been reported. Immunohistochemical (IHC) studies revealed that enteroendocrine cells did not express detectable levels of type 2 IP3 receptors, whereas nearly all enteroendocrine cells that produced chromogranin A and/or serotonin expressed type 1 and type 3 IP3 receptors. Conversely, enteroendocrine cells that produced glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, cholecystokinin, or somatostatin did not express detectable levels of any IP3 receptors. Subsets of enteroendocrine cells that produced substance P or secretin expressed type 1 (33% or 18%, respectively) and type 3 (10% or 62%, respectively) IP3 receptors. Thus, different subtypes of enteroendocrine cells, as well as individual cells that express a particular hormone, exhibit remarkable heterogeneity in the molecular machineries that regulate hormone release in vivo. These results suggest that therapeutic agents can be developed that could potentially inhibit or promote secretion of hormones from specific subtypes of enteroendocrine cells.
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PMID:Individual subtypes of enteroendocrine cells in the mouse small intestine exhibit unique patterns of inositol 1,4,5-trisphosphate receptor expression. 1468 17

Islet cell tumors of the pancreas are uncommon, and nonfunctioning tumors are even rarer than functioning ones. We report the case of a 67-year-old woman with a small nonfunctioning islet cell tumor, 6 x 5 mm in diameter, which was detected incidentally by ultrasonography, and subsequently confirmed by double-helical computed tomography. Diagnosis was established by histopathological examination after 80% distal pancreatectomy with splenectomy, and by various laboratory tests. Histologically, the islet cell tumor showed highly cellular spindle or epithelioid cells, which were positive for Grimelius stain. Immunohistochemical examination revealed that the tumor cells were positive for chromogranin A, but negative for somatostatin, insulin, glucagon, and gastrin. Its small size, location, and benignity make this a very rare type of nonfunctioning islet cell tumor.
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PMID:Small nonfunctioning islet cell tumor in the body of the pancreas: report of a case. 1474 24

The rat insulinoma cell line RINm5F, an insulin secreting pancreatic beta cell line, has been used as an attractive model for basic studies of the mechanisms of insulin secretion and, more recently, as a model for the development of alternative methods for the treatment of diabetes. To elucidate the cytological properties and expression patterns of hormones of the gastro-entero-pancreatic system, suspensions of RINm5F cells were investigated by various methods including immunocytochemistry on serial semithin sections, quantitative immunocytochemistry, routine electron microscopy, immuno-electron microscopy, in situ hybridization, and TUNEL technique. At the ultrastructural level, several phenotypes of RIm5F cells were characterized by differences in the number, shape, size, and density of their secretory granules. The most common type contained a mixture of round granules varying in size and electron density. A second type predominantly contained relatively large, moderately dense granules. Moreover, a minority of cells was characterized by the occurrence of polymorphous electron dense granules or the complete absence of any secretory granules. The immunohistochemical data showed that, among the established islet hormones, insulin was present in more than 50% of cells, whereas glucagon and somatostatin occurred only sporadically. Though cells positive for pancreatic polypeptide (PP) were not found, PP-related peptides (NPY and PYY) however could be detected in a minority of cells. The great majority of RINm5F cells were immunoreactive for chromogranin B (CgB), followed by insulin, chromogranin A (CgA), and serotonin (5-HT). In addition to intercellular differences in the density of immunostaining, numerous colocalizations of immunoreactivities were found, suggesting that RINm5F cells represent a mixture of subtypes concerning the individual pattern of hormone expression. The present results reveal a wide range of heterogeneity with respect to the morphology and especially the hormone content between individual RINm5F cells.
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PMID:Cytological and immunocytochemical characterization of the insulin secreting insulinoma cell line RINm5F. 1512 25

The regional distribution and relative frequency of neurohormonal peptides-producing cells were demonstrated in the gut of the stomachless teleost, Zacco platypus (Temminck et Schegel), using 10 types of specific antisera raised against mammalian regulatory peptides. The gut of Z. platypus was divided into five portions from proximal to distal (segment I-V). Most of immunoreactive cells in the epithelial lining portion, between epithelial cells, were generally spherical or spindle shape having long cytoplasmic process that was reached via the lumen while cells round in shape were found in the basal portions of epithelial lining occasionally. Serotonin-, somatostatin-, glucagon-, cholecystokinin (CCK)-8 and pancreatic polypeptide (PP)-immunoreactive cells were observed in this study. However, no chromogranin A-, secretin-, vasoactive intestinal peptide (VIP)-, substance P- and bombesin-immunoreactive cells were found. Serotonin-immunoreactive cells were demonstrated throughout the entire gut tract and occurred more frequently than other cells. Somatostatin-immunoreactive cells were restricted to proximal segments of the gut (segment I-III) with rare frequencies, and glucagon-immunoreactive cells were demonstrated in the proximal segments of the gut (segment I, II) with moderate to few occurrences. CCK-8-immunoreactive cells were found throughout the whole intestinal tract except for most proximal segment (segment I) with moderate to few frequencies and PP-immunoreactive cells were demonstrated in the proximal to middle segments, segment I-III, with a few, rare and rare frequencies, respectively.
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PMID:Immunohistochemical study on the endocrine cells in gut of the stomachless teleost, Zacco platypus (Cyprinidae). 1523 12

Small cell carcinomas of the uterine cervix are rare tumors with an aggressive behavior. Although these tumors can exhibit neuroendocrine differentiation, the criteria for neuroendocrine differentiation are subjective and not well defined. In this study, the authors tentatively defined small cell neuroendocrine carcinoma (SCNEC) as a tumor composed of small cells with at least two of the following: argyrophilic cytoplasm, chromogranin A immunoreactivity, and synaptophysin immunoreactivity. We found 10 cases fulfilling these requirements. Five of the 10 tumors were composed mainly of small ("oat") cells and 5 of mainly larger "intermediate" cells. The majority of both subtypes showed an insular pattern. Three of the 10 SCNECs were pure, whereas the other seven were mixed with adenocarcinoma and/or squamous cell carcinoma or cervical intraepithelial neoplasia. In addition to the definitional markers noted earlier, the tumors were immunoreactive for serotonin (6 cases), somatostatin, gastrin, glucagon, and pancreatic polypeptide. No tumors were immunoreactive for cytokeratin 20. Human papillomavirus (HPV)-18 was detected in all of the pure tumors and both the SCNEC and adenocarcinomatous components in four of the mixed tumors. No other types of HPV were detected. The tumors showed a relatively low frequency of loss of heterozygosity for representative tumor suppressor gene sites; p53 mutations were found in only one case.
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PMID:Small cell neuroendocrine carcinomas of the uterine cervix: a histological, immunohistochemical, and molecular genetic study. 1538 6

We report a case of a huge endocrine tumor of the pancreas. A 76-year-old woman was admitted for a left upper abdominal mass. She showed neither hormonal symptoms nor abnormal serum hormone levels. Ultrasound imaging showed that a heterogeneously solid and partly calcified tumor was located in the retroperitoneal space. Computed tomography showed a hypervascular tumor with central degeneration. Open laparotomy revealed that the tumor originated from the pancreas; it was removed in a mass including the spleen and the pancreatic body and tail. The resected specimen demonstrated that the 580-g tumor was multi-lobulated, encapsulated, and 14 x 14 x 7 cm in size. Microscopically, the tumor consisted of cuboidal cells with round nuclei; the cells formed palisade and trabecular structures. Immunohistologically, chromogranin A, neuronspecific enolase, and glucagon were positive only for the tumor cells. Final diagnosis was endocrine tumor of the pancreas immunohistochemically producing glucagon. No tumor recurrence has been found 3 years after the surgery. We conclude that huge tumors in the retroperitoneal space must be differentiated from nonfunctioning endocrine tumors of the pancreas because the clinical course is markedly different.
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PMID:Huge endocrine tumor of the pancreas. 1575 51

We have investigated the effects of chronically elevated glucose concentrations on the pancreatic alpha-cell line alphaTC1-6. We show that basal glucagon secretion and proglucagon gene expression were increased in response to high glucose levels. The extent of acute stimulated secretion of glucagon was also increased in response to high glucose, as was the transcription of the prohormone processing enzymes PC1/3 and PC2. The secretion of GLP-1, a proglucagon-derived peptide produced by cleavage of proglucagon by PC1/3, was also increased in response to high glucose. Gene expression profiling experiments showed that a number of components of the regulated secretory pathway were up-regulated at high glucose concentrations, including processing enzymes and exocytotic proteins. Immunoblot analysis showed that the expression of the exocytotic SNARE proteins, as well as that of PC1/3, chromogranin A, and 7B2, were all increased after chronic exposure to high glucose levels. Immunocytochemistry showed no changes in the expression of the mature alpha-cell markers glucagon and brn-4 and no induction of the immature alpha-cell marker pdx-1. We conclude that chronically elevated glucose concentrations up-regulate the regulated secretory response of the alpha-cell.
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PMID:Glucose dependence of the regulated secretory pathway in alphaTC1-6 cells. 1599 47

Expression of the cellular prion protein (PrP(c)) has been shown to be crucial for the development of transmissible spongiform encephalopathies and for the accumulation of the disease-associated conformer (PrP(sc)) in the brain and other tissues. One of the emerging hypotheses is that the conversion phenomenon could take place at the site where the infectious agent meets PrP(c). In this work we have studied whether PrP(c), a protein found predominantly in neurons, could also exist in pancreatic endocrine cells since neuroectoderm-derived cells and pancreatic islet cells share a large number of similarities. For this purpose we have examined the expression of PrP(c) in a series of fetal and postnatal bovine pancreatic tissue by immunohistochemistry and RT-PCR. Using immunostained serial sections and specific antibodies against bovine PrP(c), insulin, glucagon, somatostatin, chromogranin A and chromogranin B we found that PrP(c) is highly expressed in all endocrine cells of fetal and adult pancreatic islets with a particular strong expression in A-cells. Moreover it became evident that the PrP(c) gene-neighbour chromogranin B as well as chromogranin A are coexpressed together with PrP(c). The selective expression of PrP(c) in the bovine endocrine pancreas is of particular importance regarding possible iatrogenic transmission routes and demonstrates also that bovine pancreatic islet cells could represent an interesting model to study the control of PrP-gene expression.
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PMID:The normal cellular prion protein (PrPc) is strongly expressed in bovine endocrine pancreas. 1620 84

In view of the importance of molecular sensing in the function of the gastrointestinal (GI) tract, we assessed whether signal transduction proteins that mediate taste signaling are expressed in cells of the human gut. Here, we demonstrated that the alpha-subunit of the taste-specific G protein gustducin (Galpha(gust)) is expressed prominently in cells of the human colon that also contain chromogranin A, an established marker of endocrine cells. Double-labeling immunofluorescence and staining of serial sections demonstrated that Galpha(gust) localized to enteroendocrine L cells that express peptide YY and glucagon-like peptide-1 in the human colonic mucosa. We also found expression of transcripts encoding human type 2 receptor (hT2R) family members, hT1R3, and Galpha(gust) in the human colon and in the human intestinal endocrine cell lines (HuTu-80 and NCI-H716 cells). Stimulation of HuTu-80 or NCI-H716 cells with the bitter-tasting compound phenylthiocarbamide, which binds hT2R38, induced a rapid increase in the intracellular Ca2+ concentration in these cells. The identification of Galpha(gust) and chemosensory receptors that perceive chemical components of ingested substances, including drugs and toxins, in open enteroendocrine L cells has important implications for understanding molecular sensing in the human GI tract and for developing novel therapeutic compounds that modify the function of these receptors in the gut.
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PMID:Colocalization of the alpha-subunit of gustducin with PYY and GLP-1 in L cells of human colon. 1672 27


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