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

High-performance liquid chromatography-purified 125I-vasoactive intestinal peptide (VIP) bound to T-47D human breast cancer cells in a specific, saturable, and reversible manner. Scatchard plots were compatible with the presence of one class of VIP receptors with high affinity (Kd = 4.5 X 10(-10) M VIP, and Bmax = 293 fmol/mg protein). The neuropeptide and its natural analogues inhibited the binding of 125I-VIP and stimulated cyclic AMP (cAMP) generation in T-47D cells 96-fold (EC50 = 7 X 10(-10) M VIP), in the following order of potency: VIP greater than helodermin greater than human peptide with N-terminal histidine and C-terminal methionine greater than human pancreatic growth hormone-releasing factor greater than human secretin. In contrast, 125I-VIP binding was not displaced by pancreatic glucagon, human oxyntomodulin, truncated glucagon-like peptide-1, glucagon-like peptide-2, the somatostatin analogue SMS 201-995, gastric inhibitory peptide, and a series of steroid hormones or peptides unrelated to VIP. VIP also increased cAMP generation in seven other human breast cancer cell lines: H4-66B, HSL 53, HSL 78, MCF 7, MDA-MB231, T-47D2, and ZR75-1. Adenylate cyclase activity rose from 72.2 +/- 14 to 1069 +/- 66 pmol cAMP/min mg protein after the addition of 10(-7) M VIP to T-47D plasma membranes. In agreement with our pharmacological results and the Scatchard analysis of the binding data, sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the solubilized receptor in the T-47D membranes permitted identification of one autoradiographic band with a molecular weight of 69,000. The sensitivity of the Mr 69,000 binding site to GTP and low doses of VIP implies that in T-47D cells, this component constitutes the membrane domain involved in the functional regulation of adenylate cyclase by VIP receptors. Our results indicate a role for the VIP receptor-cAMP system in human breast cancer cells.
Cancer Res 1988 Sep 15
PMID:Pharmacology, molecular identification and functional characteristics of vasoactive intestinal peptide receptors in human breast cancer cells. 284 44

We report a case of pancreatic tumour metastatic to the liver in a patient with insulin-treated diabetes, anaemia, cheilitis, necrolytic migratory erythema, hypokalemia and chronic watery diarrhea, a picture suggesting combined glucagonoma and VIPoma syndromes. Immunocytochemistry of a biopsied hepatic metastatic nodule revealed both glucagon and vasoactive intestinal peptide (VIP) positive cells. Increased plasma glucagon and VIP levels were detected (values of 900 pmol/l and 277 pmol/l respectively). This is the first reported case showing not only immunocytochemical, but also clinical evidence of the combined secretion of these hormones.
Cancer 1988 Dec 15
PMID:A combined glucagonoma and VIPoma syndrome. First pathologic and clinical report. 284 62

A 46-year-old man had a 7-year history of severe rash, which was then diagnosed as necrolytic migratory erythema. He had a weight loss of 6 kg, abnormal glucose tolerance test findings, anemia, glossitis, hair loss, and hypoproteinemia. Plasma amino acids levels were significantly decreased, and the fasting plasma glucagon (IRG) level was high at 5000 to 8000 pg/ml. Circulating IRG significantly increased after oral glucose loading, meal ingestion, and arginine infusion, and decreased with somatostatin infusion and insulin-induced hypoglycemia. No other gut or pancreatic hormone levels in plasma were elevated. Plasma IRG was eluted by gel-filtration, mainly in the position of true glucagon (MW 3500) by antiserum 30K. The rash was markedly improved after infusion of amino acids. Computerized tomography (CT) scan and celiac angiography revealed a large pancreatic tumor with multiple liver and lymph node metastases. The pancreatic tumor was totally resected, and was identified as glucagonoma by immunohistochemical technique. Since the plasma IRG levels remained high after surgery, the patient received dimethyltriazenoimidazole carboxamide therapy. After several courses of this treatment, plasma IRG levels decreased to 1000 to 2000 pg/ml, and the hepatic metastases were remarkably diminished in size.
Cancer 1986 Feb 15
PMID:A functional study of a case of glucagonoma exhibiting typical glucagonoma syndrome. 286 23

Twenty-one days after s.c. subscapular transplantation of a radiation-induced insulinoma, male NEDH rats exhibited hyperinsulinaemia and hypoglycaemia. These features were associated with islet atrophy, degenerative changes in pancreatic A and B cells, and decreases in the pancreatic contents of insulin, glucagon and somatostatin. The immunoreactive glucagon and somatostatin contents of extrapancreatic tissues of insulinoma-bearing rats were unchanged. Surgical resection of the tumour resulted in an immediate fall of plasma insulin, attaining concentrations similar to those of anaesthetised control rats by 10 min. The estimated half-life of insulin was 3.5 min. Hypoglycaemia persisted until 60 min after resection, followed by hyperglycaemia of 1-2 days duration. Glucose tolerance was impaired 1 day after tumour resection despite the coexistence of raised insulin concentrations. Evidence for abnormal pancreatic B cell function was gained by injection of arginine which failed to evoke a plasma insulin response in the resected rats. Two days after resection, plasma glucose and insulin concentrations were similar to those of control rats. Plasma glucose and insulin responses to glucose and arginine were suggestive of tumour recurrence by 12 days. A single large encapsulated tumour was eventually observed in each rat, with resection giving a 17-56 day prolongation of life.
Br J Cancer 1986 Oct
PMID:Effects of transplantation and resection of a radiation-induced rat insulinoma on glucose homeostasis and the endocrine pancreas. 287 84

This case report deals with a patient who presented with 17 small carcinoid tumors of the rectum, the largest measuring less than 1 cm in diameter. After a review of the literature on this subject, this case is believed to be highly unusual in several respects: (1) despite their small size, these tumors resulted in multiple metastases to the regional lymph nodes; (2) both primary tumors and metastases were extensively and strongly argentaffin; and (3) most tumors and metastases contained, when investigated by immunocytochemistry, several biologically active substances such as serotonin, somatostatin, and glucagon-like immunoreactivity.
Cancer 1987 Oct 15
PMID:Multiple malignant rectal carcinoid tumors with immunocytochemical demonstration of multiple hormonal substances. 288 27

One hundred four endocrine tumors found in the body and tail of the pancreas of a patient with the Zollinger-Ellison syndrome (ZES) and multiple endocrine neoplasia (MEN-I) were investigated by immunohistochemistry for insulin, glucagon, somatostatin, pancreatic polypeptide (PP), and gastrin. The results for each tumor were scored into six grades according to the frequency of immunoreactive cells. Pancreatic polypeptide, glucagon, insulin, and somatostatin were demonstrated in 96, 80, 62, and 42 tumors, respectively. When only the higher scores of cell frequency (3-5) were considered, PP and glucagon (accounting for 71 and 49 tumors, respectively) differed markedly from insulin (two tumors) and somatostatin (0). The frequency of PP-immunoreactive cells was higher in tumors of large size whereas that of glucagon cells was higher in the smaller neoplasms. No significant associations of the tumoral hormonal expressions were found with the type of histologic structure (trabecular versus gyriform), the occurrence of stromal fibrosis, and the intrapancreatic location of the neoplasms, except for a higher number of somatostatin cells in fibrotic tumors. Gastrin-immunoreactive cells never were found in the tumors in spite of the concomitant hypergastrinemia. In conclusion, the nonrandom expression of the hormonal phenotype by the neoplastic islet cells, as shown by the immunohistochemical, semiquantitative analysis of a large number of tumors, suggests that in our MEN-I patient the genetically determined neoplasms also are affected by other mechanisms, possibly nongenetic.
Cancer 1988 May 01
PMID:Nonrandom expression of polypeptide hormones in pancreatic endocrine tumors. An immunohistochemical study in a case of multiple islet cell neoplasia. 289 80

A 28-year-old woman presented with hypoglycemia and acromegaly associated with pituitary sellar enlargement. Preoperative plasma levels of insulin and growth hormone (GH) were markedly elevated and there was mild hyperprolactinemia. Laboratory tests suggested hyperparathyroidism. Partial pancreatectomy was performed and two tumors were found. Morphologic examination revealed two well-differentiated pancreatic endocrine neoplasms with distinct histologic, immunohistochemical, and ultrastructural features. Immunoreactivity for insulin was present in the larger tumor; the smaller tumor contained glucagon, gastrin, somatostatin, and pancreatic polypeptide. Both neoplasms demonstrated growth hormone-releasing hormone (GRH) immunopositivity and released GRH in vitro. Subsequent studies confirmed abnormally elevated preoperative plasma levels of GRH. Postoperatively, blood glucose, insulin, GRH, and GH normalized and there was regression of acromegalic features with significant reduction in sellar size. The clinicopathologic findings indicate that, in patients with multiple endocrine neoplasia type I (MEN-I), GRH production by pancreatic tumors can stimulate hypophysial somatotrophs resulting in GH excess and acromegaly due to a reversible pituitary lesion, most likely somatotroph hyperplasia.
Cancer 1988 Jul 15
PMID:Reversible sellar enlargement due to growth hormone-releasing hormone production by pancreatic endocrine tumors in a acromegalic patient with multiple endocrine neoplasia type I syndrome. 289 85

The presence of a number of regulatory peptides (bombesin, gastrin, glucagon, somatostatin, calcitonin and ACTH) was compared in 30 typical carcinoid tumours and 27 well differentiated neuroendocrine carcinomas (atypical carcinoids) using conventional immunocytochemistry. Strong immunostaining for one or more peptide was observed in 97% of the typical carcinoids (29/30) whereas only 67% of the neuroendocrine carcinomas showed immunoreactivity. The peptide most frequently detected in typical carcinoids was bombesin (67%), while gastrin was more common in neuroendocrine carcinomas (44%). Immunoreactivity for more than one peptide was present in 33 tumours and in three cases, six different peptides were detected. The study shows that immunoreactivity to various peptides is more common in typical carcinoids than well differentiated neuroendocrine carcinomas. The significance of these findings is discussed.
Br J Cancer 1988 Dec
PMID:Immunoreactivity of various peptides in typical and atypical bronchopulmonary carcinoid tumours. 290 52

One hundred twenty-seven insulinomas from 95 cases (1 malignant and 94 benign) were studied pathologically. Thirty-six tumors (35 cases) were examined by electron microscopy. Typical beta-cell secretory granules of crystalloid-form cores and/or atypical secretory granules were discerned in all tumors examined. A new type of secretory granule, with high electron-dense crystalloid-form cores and moderate electron-dense granular substance filling the space between the core and the limiting membrane, were observed in two cases. Among 68 insulinomas (67 cases) subjected to immunocytochemical investigations with ten peptide hormones (insulin, glucagon, somatostatin, pancreatic polypeptide (PP), gastrin, motilin, secretin, vasoactive intestinal polypeptide (VIP), gastric inhibitory polypeptide (GIP), and neurotensin), 42 were found to be multihormonal, varying from two to four peptides secreted. The hormones contained were insulin, glucagon, PP, somatostatin, and gastrin in different combinations. One patient had hyperinsulinemia and hypergastrinemia concurrently, and two islet tumors were excised at an interval of 10 months. Both electron microscopy and immunocytochemistry confirmed the presence of beta- and alpha-cells in the first tumor, whereas the second tumor revealed only G-cells by electron microscopy, and G- and beta-cells on immunocytochemical staining. The morphologic and immunocytochemical characteristics of the insulinomas in this series are discussed.
Cancer 1985 Sep 15
PMID:Insulinoma. An immunocytochemical and morphologic analysis of 95 cases. 299 37

Twelve islet cell tumors and one islet cell hyperplasia were studied with immunocytochemical and radioimmunoassay methods. With immunocytochemical staining, all six insulinomas, one mixed insulinoma-glucagonoma, and four gastrinomas were positive for insulin, insulin and glucagon, and gastrin, respectively. Pancreatic polypeptide (PP) was positive in three insulinomas and one mixed insulinoma-glucagonoma. All of the tumors were positive for neuron-specific enolase (NSE). Radioimmunoassays of tissue extracts further disclosed that all functioning tumors contained more than one pancreatic hormone. PP concentrations of two insulinomas and one mixed insulinoma-glucagonoma were higher than that of normal control pancreases. A study of protein meal-stimulated PP secretion revealed that three of the insulinoma cases and two gastrinoma cases exhibited higher plasma PP levels than the age-matched controls. The findings suggest that: both functioning and nonfunctioning islet cell tumors derive from neuroendocrine cells positive for NSE; all functioning islet cell tumors appear to contain PP in the tumor tissue as a minor component; as many as 70% of the patients with islet cell tumors present with abnormally higher plasma PP levels after protein meals; and a study of meal-stimulated PP secretion may well be used as a marker for the presence of functional islet cell tumors.
Cancer 1985 Oct 01
PMID:Pancreatic polypeptide in islet cell tumors. Morphologic and functional correlations. 299 43


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>