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)

Few cases of malignant glucagonomas have been described in the literature. In this paper we present a case of a 77-year-old woman with necrolytic migratory erythema and high plasma glucagon and chromogranin A levels caused by a neuroendocrine tumour. An abdominal CT scan suggested a pancreatic lesion and two liver metastases. The patient underwent pancreatic debulking and liver metastasectomy. Histological and immunohistochemical investigations revealed a well differentiated neuroendocrine tumour with vascular invasion and scattered immunopositivity for somatostatin receptors. The patient was treated with octreotide (20 mg i.m. every 28 days) for three years without side effects. Three months after surgery symptoms of disease recurred accompanied by hyperglucagonaemia and newly diagnosed liver lesions. The patient was treated with octreotide (30 mg i.m. every 28 days) and interferon-alpha (6 MU s.cc 3 times per week) plus three cycles of hepatic chemoembolisation. Symptoms resolved after the first month of therapy, hormone levels decreased compared to untreated levels and metastatic growth slowed as observed by radiographic evidence. The patient is now asymptomatic with persistent hepatic disease and normal serum glucagon levels forty months after primary treatment. So far, only few immunohistochemical studies are reported on malignant glucagonoma and combined treatment schedules. We demonstrated, for the first time, a scattered immunopositivity for somatostatin receptors in a malignant glucagonoma. For this reason, the somatostatin analogs therapy was instituted. A combined antiproliferative medical treatment and the hepatic chemoembolization have been able to control tumor growth and disease symptoms for a long time after surgery.
 ...
PMID:Malignant glucagonoma. New options of treatment. 1676 30

Herein is presented the case of a malignant non-functioning endocrine tumor of the pancreas with oncocytic features, and a discussion on the high incidence of malignancy in oncocytic endocrine pancreatic tumors. The patient was a 65-year-old woman who showed no paraneoplastic symptoms produced by functioning pancreatic endocrine tumors. The primary tumor was located in the body and tail of the pancreas, and had metastasized to the liver. Tumor cells were arranged in a ribbon-like or trabecular pattern and had an abundant eosinophilic cytoplasm containing numerous mitochondria and neurosecretory granules. The cytoplasm of the tumor cells was intensely stained with an antimitochondrial antigen antibody. Most tumor cells stained positively with Grimelius stain and for chromogranin A. Some tumor cells also stained for synaptophysin. However, the tumor cells negatively stained for hormones such as insulin, glucagon, somatostatin, gastrin, vasoactive intestinal peptide and pancreatic polypeptide, for serotonin, and for pancreatic enzymes such as amylase and trypsin. Analysis of 18 oncocytic pancreatic endocrine tumors, consisting of those reported previously and that in the present case, suggests that the high incidence of malignancy in oncocytic endocrine tumors is associated with the high incidence of non-functioning endocrine tumors among them, most of which are malignant.
 ...
PMID:Oncocytic non-functioning endocrine tumor of the pancreas. 1709 34

A carcinoid tumor was found as a solitary soft mass in the wall of the rectum adjacent to the anorectal junction in an adult Holstein cow. Microscopically, the tumor involved the submucosa and partly invaded the muscular layer. It consisted of a compact arrangement of a great number of large polygonal cells and a small number of small dark cells, some of which showed argyrophilia (Grimelius positive). Immunohistochemically, both types of tumor cells were positive for vimentin, keratin, and S-100 protein and weakly positive for neuron-specific enolase (NSE), whereas they were negative for some endocrine markers such as chromogranin A, insulin, glucagon, somatostatin, serotonin, adrenocorticotropic hormone, and calcitonin. Electron microscopy revealed membrane-bound secretory granules in the cytoplasm of some small dark cells. In such a poorly differentiated carcinoid, the morphologic characteristics of the small dark cells were strong evidence for the diagnosis. This is the first description of a poorly differentiated carcinoid developing in the rectum of a cow.
 ...
PMID:Poorly differentiated rectal carcinoid in a cow. 1749 Oct 91

Type 1 diabetes is resulting from the selective destruction of insulin-producing betacells within the pancreatic islets. Somatostatin acts as an inhibitor of hormone secretion through specific receptors (sst1-5). All ssts were expressed in normal rat and mouse pancreatic islets, although the expression intensity and the co-expression pattern varied between ssts as well as between species. This may reflect a difference in response to somatostatin in islet cells of the two species. The Non-Obese Diabetic (NOD) mouse model is an experimental model of type 1 diabetes, with insulitis accompanied by spontaneous hyperglycaemia. Pancreatic specimens from NOD mice at different age and stage of disease were stained for ssts. The islet cells of diabetic NOD mice showed increased islet expression of sst2-5 compared to normoglycemic NOD mice. The increase in sst2-5 expression in the islets cells may suggest either a contributing factor in the process leading to diabetes, or a defense response against ongoing beta-cell destruction. Somatostatin analogues were tested on a human endocrine pancreatic tumour cell line and cultured pancreatic islets. Somatostatin analogues had an effect on cAMP accumulation, chromogranin A secretion and MAP kinase activity in the cell line. Treatment of rat pancreatic islets with somatostatin analogues with selective receptor affinity was not sufficient to induce an inhibition of insulin and glucagon secretion. However, a combination of selective analogues or non-selective analogues via costimulation of receptors can cause inhibition of hormone production. For insulin and glucagon, combinations of sst2 + sst5 and sst1 + sst2, respectively, showed a biological effect. In summary, knowledge of islet cell ssts expression and the effect of somatostatin analogues with high affinity to ssts may be valuable in the future attempts to influence beta-cell function in type 1 diabetes mellitus, since down-regulation of beta-cell function may promote survival of these cells during the autoimmune attack.
 ...
PMID:Somatostatin receptor expression and biological functions in endocrine pancreatic cells: review based on a doctoral thesis. 1757 4

Cases of acromegaly due to GHRHproducing pancreatic endocrine tumors have been reported. Here we present a case of a 31-yr-old nonacromegalic man with hyperparathyroidism and elevated serum IGF-I with normal serum GH levels. Serum GH was not suppressed below 1 ng/ml by the glucose tolerance test and increased in response to TR H and GHRH administration. Magnetic resonance imaging (MRI) revealed pituitary hyperplasia and an abdominal computed tomography (CT ) scan showed a tumor in the pancreatic tail. Plasma concentration of GHRH was elevated. Based on these clinical data, multiple endocrine neoplasia (MEN) type 1 was suspected. Three enlarged parathyroid glands were removed and a distal pancreatectomy was performed. Pathological examination of the parathyroid glands and pancreatic tumor showed nodular hyperplasia and a well-differentiated endocrine tumor, respectively, both compatible with MEN features. Immunohistochemistry revealed positive immunoreactivity for GHRH, SS , insulin, glucagon, chromogranin A, and pancreatic polypeptide in the pancreatic tumor. After pancreatic surgery, elevated levels of GHRH and IGF-I were normalized and pituitary hyperplasia definitely decreased in size. In cases of pituitary hyperplasia with elevated IGF-I, ectopic GHRH syndrome must be considered even if physical features of acromegaly are absent. It is also important to measure plasma GHRH concentrations in order to give a diagnosis.
 ...
PMID:A non-acromegalic case of multiple endocrine neoplasia type 1 accompanied by a growth hormone-releasing hormone-producing pancreatic tumor. 1759 76

Clusterin is a well-known glycoprotein expressed by many cell types involved in multiple physiological functions. In rat pancreatic tissue it is expressed along with islet cell development and found to be involved in regeneration of pancreatic endocrine cells after various types of tissue injuries. These results led us to propose that clusterin might play a crucial role in organization and assembling processes of islet cells during pre- and postnatal development. Therefore, the aim of this study was to find out whether and in which cell type clusterin is expressed during islet cell organization in the porcine species which could play a future role in the field of xenotransplantation. For this purpose we examined the expression pattern of clusterin at different developing stages in the porcine pancreas by double-immunostaining with antibodies against chromogranin A and clusterin, and clarified whether distinct islet hormones were coexpressed with clusterin. Further, we checked by RT-PCR whether clusterin was locally expressed or possibly locally bound to the corresponding receptor. In newborn and up to 3-month-old animals clusterin was found to be expressed in a special cell type which is closely associated and intermingled with other endocrine cells. In fully developed adult islets clusterin-cells then reorganize and were found to be mainly localized in the mantle area of Langerhans islets. Double-immunostaining with antibodies against clusterin and different islet hormones such as insulin, glucagon, and somatostatin clearly demonstrate that clusterin expression was found in an own special cell type and it is also present in a subset of glucagon producing A-cells. Taken together, our results show that clusterin expression in porcine species is found in an own, as yet unidentified cell type during postnatal developmental stages, and probably labels immature precursor cells in adult animals, which finally have the potential to differentiate into glucagon-expressing cells.
 ...
PMID:Clusterin expression in porcine endocrine cells during islet development. 1796 May 12

Both ghrelin and obestatin are derived from preproghrelin by post-translational processing. We have morphologically characterized the cells that produce obestatin and ghrelin in new-born and adult Sprague-Dawley rats that were freely fed, fasted, or subjected to gastric bypass surgery or reserpine treatment. Tissue samples collected from the gastrointestinal tract and pancreas were examined by double-immunofluorescence staining, immunoelectron microscopy, and conventional electron microscopy. Obestatin was present in the stomach, duodenum, jejunum, colon, and pancreas. In the stomach, differences were noted in the development of obestatin- and preproghrelin-immunreactive (IR) cells on the one hand and ghrelin-IR cells on the other, particularly 2 weeks after birth. Preproghrelin- and obestatin-IR cells were more numerous than ghrelin-IR cells in the stomach, suggesting the lack of ghrelin in some A-like cells. Most obestatin-producing cells in the stomach were distributed in the basal part of the oxyntic mucosa; these cells co-localized with chromogranin A (pancreastatin) and vesicle monoamine transporters type 1 and 2, but not with serotonin or histidine decarboxylase. Immunoelectron microscopy revealed the obestatin- and ghrelin-producing cells to be A-like cells, characterized by numerous highly electron-dense granules containing ghrelin and obestatin. Some granules exhibited an even electron density with thin electron-lucent halos, suggestive of monoamines. Feeding status, gastric bypass surgery, and reserpine treatment had no obvious effect on the A-like cells. In the pancreas, obestatin was present in the peripheral part of the islets, with a distribution distinct from that of glucagon-producing A cells, insulin-producing beta cells, and cells producing pancreatic polypeptide Y. Thus, obestatin and ghrelin co-localize with an anticipated monoamine in A-like cells in the stomach, and obestatin is found in pancreatic islets.
 ...
PMID:Characterization of obestatin- and ghrelin-producing cells in the gastrointestinal tract and pancreas of rats: an immunohistochemical and electron-microscopic study. 1807 56

Numerous studies conducted in a diversity of adult tissues have shown that certain stem cells are characterized by the expression of a protein known as the ABCG2 transporter (where ABC is ATP- binding cassette). In the adult pancreas, although various multipotent progenitors have been proposed, the ABCG2 marker has only been detected in the so-called 'side population' (a primitive haematopoietic cell population with a multipotential capacity). In the present study we sought to identify new ABCG2+ pancreatic cell populations and to explore whether they exhibit the properties of progenitor cells. We isolated and expanded mitoxantrone-resistant cells from pancreata of lactating rats by drug selection. These cells were characterized and maintained in different stages of differentiation using several media 'cocktails' plus Matrigel (BD Biosciences). Differentiation was assessed by RT-PCR (reverse transcription-PCR), immunocytochemistry, electron microscopy and ELISA. The expanded cell population demonstrated a phenotype of PaSCs (pancreatic stellate cells). Spontaneous cell clusters occurred during cell expansion and they showed weak expression of the transcription factor Pdx1 (pancreatic and duodenal homeobox 1). Moreover, the presence of inductive factors in the Matrigel plus exendin-4 led to an increase in Pdx1 and endocrine genes, such as insulin, islet amyloid polypeptide, glucagon, the glucose transporter GLUT2, chromogranin A and the convertases PC1/3 and PC2 were also detected. Immunocytochemical analysis showed co-localization of insulin and C-peptide, whereas ultrastructural studies revealed the presence of granules. Insulin secretion from cell clusters was detected in the cell culture medium. We identified a population of PaSCs that express the ABCG2+ transporter and have the capacity to transdifferentiate into insulin-producing cells. Although the potential therapeutic application remains to be tested, PaSCs could represent a future option for insulin replacement in diabetes research.
 ...
PMID:Identification of a pancreatic stellate cell population with properties of progenitor cells: new role for stellate cells in the pancreas. 1955 23

A 65-year-old Japanese male was referred to our hospital for evaluation of a main pancreatic duct obstruction. Two months previously, he had suffered an attack of acute pancreatitis that was resolved with conservative treatment. Dynamic contrast-enhanced study by multidetector row computed tomography revealed a well-enhanced 5 x 5 mm mass in the head of the pancreas with dilatation of the main pancreatic duct in the body and tail. On endoscopic retrograde pancreatography, obstruction of the main pancreatic duct in the head of the pancreas was noted. Pancreatic juice cytology was nondiagnostic. Endoscopic ultrasonography demonstrated a well-defined hypoechoic mass, about 5 mm in size, with distal main pancreatic duct dilatation. The patient underwent elective pylorus-preserving pancreaticoduodenectomy. Pathological examination revealed a well-differentiated endocrine tumor of the pancreas of uncertain behavior, 5 mm in size. Immunohistochemically, the tumor was diffusely positive for chromogranin A and synaptophysin, and focally it was positive for insulin, glucagon, and CA19-9; it was negative for gastrin. The final diagnosis was main pancreatic duct obstruction secondary to a nonfunctioning endocrine tumor of the pancreas of uncertain behavior. Of note, a small nonfunctioning endocrine tumor of the pancreas is important in the differential diagnosis of main pancreatic duct obstruction demonstrated by radiographic examinations.
 ...
PMID:Main pancreatic duct obstruction due to a small nonfunctioning endocrine tumor of the pancreas. 1940 May 56

The cDNA microarray gene profile of gastrointestinal stromal tumors (GISTs) revealed that DOG1 (TMEM16A) gene was mostly expressed in these neoplasms. Immunohistochemically, DOG1 protein was found positive in a significant proportion of GISTs. However, normal tissues' expression of DOG1 is not yet completely studied. Our study intended to identify the DOG1 protein expression in normal adult and fetal tissues, in comparison with that of GISTs, using an anti-DOG1 polyclonal serum. Fourteen CD117/CD34-positive GIST cases were tested for DOG1. Tissue samples from autopsies of 15 human fetuses and 11 adults were tested immunohistochemically on simple or double staining with antibodies raised against: DOG1, insulin, glucagon, somatostatin, NK1, PGP9.5, chromogranin A, and synaptophysin. All the tested GISTs were positive for DOG1, with a membranous and cytoplasmic location. The normal tissues showed a distinct positivity for DOG1 only in the endocrine pancreas, in both fetal and adult ones. The other tissues tested showed a weak or negative reaction. The DOG1 staining pattern in the pancreas islets was granular, like that of neuroendocrine markers. The location of DOG1 expression in pancreatic islets was partly similar to neuroendocrine markers chromogranin A, PGP9.5, and synaptophysin. The positive cells were situated centrally, in the vicinity of insulin-bearing cells as seen on double staining. DOG1 positivity in fetal and adult pancreatic islets suggests the strong antibody affinity for neuroendocrine cells. Before making a final conclusion regarding the suitability of DOG1 as a new neuroendocrine marker, a large survey of neuroendocrine lesions must be undertaken, including carcinoid tumors of various sites and pancreatic endocrine tumors. To the best of our knowledge, this particular localization has not been reported yet for DOG1.
 ...
PMID:Pancreatic expression of DOG1: a novel gastrointestinal stromal tumor (GIST) biomarker. 1941 27


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