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)

Gastroenteropancreatic (GEP) neoplasms originate from any of the various cell types belonging to the neuroendocrine system. A general characteristic of GEP endocrine tumours is that the vast majority produce and secrete a multitude of peptide hormones and amines. Many patients with malignant metastasising tumours present clinical symptoms related to hormone hyperproduction. These include the so-called carcinoid syndrome, characterised by flushing, diarrhoea, wheezing and right heart disease, which is predominantly associated with the serotonin- and tachykinins-producing carcinoids of the midgut. Several types of syndrome associated with GEP endocrine tumors are caused by overproduction of a specific hormone. For instance, the well-known Zollinger-Ellison syndrome is gastrin-mediated. The so-called 'insulinoma syndrome' depends on excessive production of insulin and proinsulin, resulting in hypoglycemia. The 'glucagonoma syndrome' is characterised by necrolytic migratory erythema, diabetes and diarrhoea. The Verner-Morrison syndrome, which is brought about by high circulating levels of vasointestinal peptide (VIP). produces severe secretory diarrhoea. Finally the 'somatostatinoma syndrome' involves gallbladder dysfunction and gallstones, diarrhoea with or without steatorrhea, and impaired glucose tolerance. The biochemical diagnosis of endocrine digestive tumors is based on general and specific markers. The best general markers are chromogranin A (CgA) and pancreatic polypeptide (PP). Specific markers for endocrine tumors include insulin, gastrin, glucagon, vaso intestinal polypeptide (VIP), somatostatin and the primary cathabolic product of serotonin, 5-hydroxyndoleacetic acid (5-HIAA). Localisation procedures commonly applied, in the diagnosis of endocrine tumours include ultrasound (US), computed tomography (CT) and somatostatin receptor scintigraphy (SRS).
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PMID:Epidemiology, clinical features and diagnosis of gastroenteropancreatic endocrine tumours. 1176 60

We report a unique case of gallbladder adenocarcinoma associated with florid neuroendocrine cell nests and extensive Paneth cell metaplasia that has not been described previously. The patient was a 79-yr-old woman with a pedunculated, polypoid mass in the gallbladder. Microscopically, the mass was composed at tumor cells showing tubular and papillary growth patterns, consistent with well-differentiated adenocarcinoma. One-third or more of the tumor cell showed Paneth cell appearance. Goblet cell-type tumors were also intermingled. In addition, neuroendocrine cell nests, that were connected to the neoplastic glands, were scattered throughout the stroma. lmmunohistochemically, the labeling index of MIB-1 in adenocarcinoma cells including Paneth cell-type carcinoma cells was approx 40%. Neuron-specific enolase, chromogranin A, and synaptophysin were positive in the neuroendocrine cells forming solid nests and intermingled within neoplastic glands. They were immunopositive for serotonin but negative for insulin, glucagon, somatostatin, and pancreatic polypeptide (PP). Although MIB-1-positive neuroendocrine cell nests were very few with weak staining, we think that the neuroendocrine cell nests were neoplastic in nature. The formation of the multifocal neuroendocrine nests may be a consequence of the trophic effects of unknown substance(s), which can promote serotonin producing neuroendocrine cells to proliferate. We postulate that Paneth cell-type carcinoma cells may be intimately related to such substance(s) in our case.
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PMID:Gallbladder Adenocarcinoma with Florid Neuroendocrine Cell Nests and Extensive Paneth Cell Metaplasia. 1211 61

Islets of Langerhans account for 2 g of endocrine tissue in the pancreas, comprising approximately one million islets, with each containing 1000 endocrine cells. The major hormone secreted from the islets is insulin, which regulates blood glucose, the main fuel of the body. Islets also secrete glucagon, somatostatin and pancreatic polypeptide and all are involved in the paracrine mechanism. Islet cells can be stained immunohistochemically for the general endocrine markers, chromogranin A, synaptophysin, neuron-specific enolase and Leu7. Beta islet cells are well equipped with glucose transporter 2, which binds to glucose and regulates diffusion of glucose through the beta cell membrane. As all four islet hormones are initially synthesized as prohormones, all islet cells are equipped with prohormone convertase 1/3 and 2. In addition, islet cells also contain zinc-containing matrix metalloproteinases and their inhibitors, metallothionein, cyclin-dependent kinases and insulin-like growth factors, and many more hormones, peptides and enzymes. Thus, islets not only secrete insulin and other pancreatic hormones but are a complex organ whose major function is glucose homeostasis.
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PMID:New markers for pancreatic islets and islet cell tumors. 1216 99

To clarify whether scattered endocrine cells in pancreatic ductal adenocarcinoma are neoplastic or not, we immunohistochemically studied 29 cases of invasive pancreatic ductal adenocarcinomas, 17 with metastases, for chromogranin A, insulin, glucagon, pancreatic polypeptide, serotonin, gastrin, laminin, and Ki-67. Endocrine cells were found in primary sites in 24 cases (82.3%), where endocrine cells showed at least a visibly close location to adjacent islet cells. Although endocrine cells in neoplastic glands were within the neoplastic basement membrane, endocrine cells were not seen in invasive sites beyond the pancreas where islets were not present. Endocrine cells in neoplastic glands were reactive for two or three of the islet hormones in all cases, and different types of hormonal reactivity was recognized in the same neoplastic gland or the same cluster of neoplastic glands in 22 (91.7%) cases, thus suggesting a close relation with islets. Ki-67 did not stain any endocrine cells in ten of the adenocarcinomas studied. In three (10.3%) cases, endocrine cells were found in the intraductal extensions. They may have pre-existed in non-neoplastic ducts. In 17 cases with metastatic sites, all but one had no endocrine cells in the metastases. Serotonin-positive cells were found in one metastatic lymph node in one case. We concluded that most endocrine cells seen in ductal adenocarcinomas of the pancreas are non-neoplastic and are derived from the surrounding islets. Some neoplastic endocrine cells may exist, though their frequency is low.
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PMID:Immunohistochemical study of endocrine cells in ductal adenocarcinoma of the pancreas. 1224 21

The regional distributions and relative frequencies of some gastrointestinal endocrine cells in the three portions (cecum, colon and rectum) of the large intestinal tract of C57BL/6 mice were examined with immunohistochemical method using 7 types of specific antisera against chromogranin A (CGA), serotonin, somatostatin, human pancreatic polypeptide (HPP), glucagon, gastrin and cholecyctokinin (CCK)-8. In this study, all 3 types of immunoreactive (IR) cells were identified. Most of these IR cells in the large intestinal portion were generally spherical or spindle in shape (open-typed cell) while cells with a round shape (close-typed cell) were found in the intestinal gland. Their relative frequencies varied according to each portion of the large intestinal tract. CGA-IR cells were found throughout the whole large intestinal tract but were most predominant in the colon. Serotonin-IR cells were detected throughout the whole large intestinal tract and showed highest frequency in the colon. Peculiarly, glucagon-IR cells were restricted to the colon with a low frequency. However, no somatostatin-, HPP-, gastrin- and CCK-8-IR cells were found in the large intestinal tract. In conclusion, some peculiar distributional patterns of large intestinal endocrine cells were identified in C57BL/6 mice.
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PMID:Regional distribution and relative frequency of gastrointestinal endocrine cells in large intestines of C57BL/6 mice. 1251 36

K cells are a subpopulation of enteroendocrine cells that secrete glucose-dependent insulinotropic polypeptide (GIP), a hormone that promotes glucose homeostasis and obesity. Therefore, it is important to understand how GIP secretion is regulated. GIP-producing (GIP/Ins) cell lines secreted hormones in response to many GIP secretagogues except glucose. In contrast, glyceraldehyde and methyl pyruvate stimulated hormone release. Measurements of intracellular glucose 6-phosphate, fructose 1,6-bisphosphate, and pyruvate levels, as well as glycolytic flux, in glucose-stimulated GIP/Ins cells indicated that glycolysis was not impaired. Analogous results were obtained using glucose-responsive MIN6 insulinoma cells. Citrate levels increased similarly in glucose-treated MIN6 and GIP/Ins cells. Thus pyruvate entered the tricarboxylic acid cycle. Glucose and methyl pyruvate stimulated 1.4- and 1.6-fold increases, respectively, in the ATP-to-ADP ratio in GIP/Ins cells. Glyceraldehyde profoundly reduced, rather than increased, ATP/ADP. Thus nutrient-regulated secretion is independent of the ATP-dependent potassium (K(ATP)) channel. Antibody staining of mouse intestine demonstrated that enteroendocrine cells producing GIP, glucagon-like peptide-1, CCK, or somatostatin do not express detectable levels of inwardly rectifying potassium (Kir) 6.1 or Kir 6.2, indicating that release of these hormones in vivo may also be K(ATP) channel independent. Conversely, nearly all cells expressing chromogranin A or substance P and approximately 50% of the cells expressing secretin or serotonin exhibited Kir 6.2 staining. Compounds that activate calcium mobilization were potent secretagogues for GIP/Ins cells. Secretion was only partially inhibited by verapamil, suggesting that calcium mobilization from intracellular and extracellular sources, independent from K(ATP) channels, regulates secretion from some, but not all, subpopulations of enteroendocrine cells.
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PMID:Studies with GIP/Ins cells indicate secretion by gut K cells is KATP channel independent. 1267 50

The regional distributions and relative frequencies of some gastrointestinal endocrine cells in the eight portions (fundus, pylorus, duodenum, jejunum, ileum, cecum, colon and rectum) of the gastrointestinal tract of C57BL/6 mouse was studied with immunohistochemical method using seven types of specific anti-sera against chromogranin A (CGA), serotonin, somatostatin, human pancreatic polypeptide (HPP), glucagon, gastrin and cholecystokinin (CCK)-8. In this study, all these seven types of immunoreactive (IR) cells were identified. Most of these IR cells in the intestinal portion were generally spherical or spindle in shape (open-type cell) while cells showing round in shape (closed-type cell) were found in the intestinal gland and stomach regions occasionally. Their relative frequencies were varied according to each portion of gastrointestinal tract. CGA-IR cells were demonstrated throughout the whole gastrointestinal tract and they showed most predominant in the pylorus and duodenum. Serotonin-IR cells were detected throughout whole gastrointestinal tract and they showed highest frequency in the stomach and colon. Somatostatin-IR cells were demonstrated throughout whole gastrointestinal tract except for large intestine and showed highest frequency in the fundus. HPP-IR cells were found in the fundus with rare frequency. Peculiarly, glucagon-IR cells were restricted to the fundus, ileum and colon with a few frequencies. Gastrin-IR cells were restricted to the pylorus with numerous frequency and CCK-8-IR cells were observed in the pylorus, duodenum and jejunum with numerous and/or a few frequencies, respectively. In conclusion, some peculiar distributional patterns of gastrointestinal endocrine cells were found in C57BL/6 mouse.
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PMID:An immunohistochemical study of the gastrointestinal endocrine cells in the C57BL/6 mice. 1273 69

A golden yellow polyp was detected in the gallbladder of a 64-year-old man who presented with epigastric pain. The lesion was composed of clear polygonal cells arranged in a trabecular and glandular pattern. The tumor invaded through the wall into the perimuscular subserosal layer. Immunohistochemical stains showed that neoplastic cells were positive for chromogranin A, synaptophysin, somatostatin, gastrin, and pancreatic polypeptide and negative for glucagon, serotonin, insulin, S100 protein, and inhibin. This tumor resembles the recently described clear cell endocrine tumors of the gallbladder and pancreas that are associated with von Hippel-Lindau disease. Our patient, however, had neither personal nor family history indicative of von Hippel-Lindau disease. Furthermore, published accounts of clear cell endocrine tumors in von Hippel-Lindau disease describe immunoreactivity for inhibin; the current case was negative for the disease. There may be a subtype of clear cell carcinoid tumor not associated with von Hippel-Lindau disease, which is characterized by its lack of immunoreactivity against inhibin.
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PMID:Clear cell carcinoid tumor of the gallbladder. A case without von Hippel-Lindau disease. 1274 4

Glucagonoma of the pancreas is a rare tumor with distinct clinical manifestations, such as necrolytic migratory erythema,weight loss, anemia, diabetes mellitus, and hypoamino-acidemia. We report the case of a 68-year-old Japanese man who underwent curative resection for malignant glucagonoma of the pancreas diagnosed through anemia and diabetes mellitus. The patient had had diabetes mellitus for 20 years. Anemia was diagnosed in 1998. On admission, the hemoglobin level was 8.3g/dl, but the levels of serum iron, vitamin B12, and erythropoietin and, the number of reticulocytes were within normal limits. The levels of carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9, and DUPAN-2 were also within normal limits, and exocrine function of the pancreas (PFD, 75%) was normal. Ultrasonography (US) revealed a hypoechoic tumor in the distal pancreas. Computed tomography (CT) demonstrated a high-density area 4 cm in diameter with calcification. The serum glucagon level was very high (2360 pg/ml), but the levels of other hormones such as somatostatin or gastrin were within normal limits, while insulin was low. Glucagonoma of the pancreas was diagnosed, and distal pancreatectomy with splenectomy was performed. Histological examination revealed a malignant endocrine tumor,which was immunohistochemically positive for chromogranin A and glucagon. Two months after the operation, the serum glucagon level had decreased to within normal limits and the hemoglobin level had increased to 10.4 g/dl. The case of glucagonoma reported here was found through diagnostic examinations of anemia and treated by surgical resection, by which the patient's anemia was largely alleviated. Therefore, we recommend checking patients who have diabetes mellitus and anemia in order to diagnose and treat glucagonoma in its early stage.
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PMID:Malignant glucagonoma of the pancreas diagnoses through anemia and diabetes mellitus. 1291 65

Glucagon-like peptide-2 (GLP-2) increases small intestinal growth and function in rodents and human subjects. GLP-2 exerts its effects through a seven-transmembrane domain, G protein-coupled receptor (GLP-2R), stimulating cAMP generation and activating protein kinase A signaling in heterologous cell lines transfected with the GLP-2R. As intestinal cell lines expressing the GLP-2R have not been identified, we developed methods for studying GLP-2R signaling in the rat small intestinal mucosa in vitro. Isolated rat intestinal mucosal cells expressed mRNA transcripts for the GLP-2R, as well as for chromogranin A and beta-tubulin III, markers for enteroendocrine and neural cells, respectively. cAMP production in response to [Gly2]GLP-2, a degradation-resistant analog of GLP-2, was maximal at 10-11 m (268 +/- 93% of control, P < 0.001), with reduced cAMP accumulation observed at higher doses. The cAMP response was diminished by pretreatment with 10-9 m GLP-2, and was abolished by pretreatment with 10-6 m GLP-2 (P < 0.05), indicating receptor desensitization. GLP-2 treatment of isolated mucosal cells increased 3H-thymidine incorporation (to 128 +/- 8% of controls, P < 0.05), and this was prevented by inhibition of the protein kinase A pathway with H89. In contrast, GLP-2 did not affect p44/p42 MAPK phosphorylation or the levels of cytosolic calcium in the mucosal cell preparation. These results provide the first evidence that activation of the endogenous rat mucosal GLP-2 receptor is linked to activation of a cAMP/protein kinase A-dependent, growth-promoting pathway in vitro.
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PMID:Glucagon-like peptide-2 receptor activation in the rat intestinal mucosa. 1296 94


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