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)

Nine human exocrine pancreatic adenocarcinomas were examined by serial sectioning and double- and triple-labeled immunohistochemical techniques with antibodies against chromogranin A, insulin, islet amyloid polypeptide, glucagon, somatostatin, pancreatic polypeptide, serotonin, pancreastatin, and neuron-specific enolase. The results were correlated with the stage of the disease, histologic characteristics of the tumors, and survival of the patients. Cells immunoreactive with most or all of the antibodies were found in all nine cases. Abnormal co-location of some hormones in the same cell and the lack of normal co-location of other hormones were found. Endocrine cells also were identified in the invasive regions of the cancer, including perineural spaces. Abnormality in the production and release of the peptide was indicated not only in the endocrine cells of exocrine cancer, but also in the islets near the cancer. Patients whose cancer contained many endocrine cells seemed to survive longer than those with tumors containing fewer endocrine cells. The overall data suggested that the observed abnormalities may contribute to the impaired glucose tolerance found in six of these patients.
 ...
PMID:Endocrine aspects of exocrine cancer of the pancreas. Their patterns and suggested biologic significance. 837 30

We previously established pluripotent transformed rat islet cell lines, MSL-cells, of which certain clones have been used to study processes of islet beta-cell maturation, including the transcriptional activation of the insulin gene induced by in vivo passage. Thus, successive sc transplantation in NEDH rats resulted in stable hypoglycemic insulinoma tumor lines, such as MSL-G2-IN. Occasionally, hypoglycemia as well as severe weight loss were observed in the early tumor passages of MSL-G and the subclone, NHI-5B, which carry the transfected neomycin and human insulin genes as unique clonal markers. By selective transplantation, it was possible to segregate stable anorectic normoglycemic tumor lines, MSL-G-AN and NHI-5B-AN, from both clones. These tumors cause an abrupt onset of anorexia when they reach a size of 400-500 mg (< 0.3% of total body weight), and the observed weight loss parallels that of starved rats until death results from cachexia. After tumor resection, animals immediately resume normal feeding behavior. Comparative studies of hormone release and mRNA content in anorectic lines, MSL-G-AN and NHI-5B-AN, vs. those in the insulinoma line, MSL-G2-IN, revealed selective glucagon gene expression in both of the anorectic tumors, whereas insulin and islet amyloid polypeptide gene expression were confined to the insulinoma. Both tumor phenotypes produced cholecystokinin and gastrin in variable small amounts, making it unlikely that these hormones contribute to the anorectic phenotype. Tumor necrosis factor (cachectin) was not produced by any of the tumors. Proglucagon was processed as in the fetal islet to products representative of both pancreatic alpha-cell and intestinal L-cell phenotypes, with glucagon and Glp-1 (7-36)amide as the major extractable products. In contrast to the administration of cholecystokinin, neither glucagon, Glp-1 (7-36)amide, nor their combination, affected feeding behavior in fasted mice, suggesting the presence of a hitherto unidentified anorectic substance released from the glucagonoma. We conclude 1) that glucagonomas and insulinomas can be derived from a common clonal origin of pluripotent MSL cells, thus supporting the existence of a cell lineage relationship between islet alpha- and beta-cell during ontogeny; and 2) that our glucagonomas release an anorexigenic substance(s) of unknown nature that causes a severe weight loss comparable to that reported in animals carrying tumor necrosis factor-producing experimental tumors.
 ...
PMID:The dissociation of tumor-induced weight loss from hypoglycemia in a transplantable pluripotent rat islet tumor results in the segregation of stable alpha- and beta-cell tumor phenotypes. 840 49

Islet amyloid polypeptide or amylin is a polypeptide secreted mainly from the pancreatic beta cells together with insulin upon stimulation. High levels of islet amyloid polypeptide have also been shown to increase the peripheral insulin resistance and consequently a role for islet amyloid polypeptide in the glucose homeostasis has been suggested. We have studied the glucose homeostasis in a patient with a malignant endocrine pancreatic tumour producing large amounts of an islet amyloid polypeptide-like molecule (about 400 times the upper reference level for islet amyloid polypeptide). This patient developed insulin-requiring diabetes mellitus shortly after the tumour diagnosis. Both intravenous and oral glucose tolerance tests revealed inhibited early responses in insulin and C-peptide release, but the insulin and C-peptide response to glucagon stimulation was less affected. Aneuglycaemic insulin clamp showed normal insulin-mediated glucose disposal. In vitro experiments, where isolated rat pancreatic islets were cultured with serum from the patient, showed a moderately decreased islet glucose oxidation rate and glucose-stimulated insulin release compared to islets cultured with serum from healthy subjects. However, culture of rat islets with normal human serum supplemented with synthetic rat islet amyloid polypeptide did not affect the glucose-stimulated insulin release. In conclusion, the observed effects show that the diabetic state in this patient was associated with an impaired glucose-stimulated insulin release but not with an increased peripheral insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Inhibition of insulin secretion, but normal peripheral insulin sensitivity, in a patient with a malignant endocrine pancreatic tumour producing high amounts of an islet amyloid polypeptide-like molecule. 840 56

We have detected islet amyloid polypeptide (IAPP)-like immunoreactivity (-LI) in human pancreas and in a range of endocrine tumors, including oat cell carcinoma of the lung and pancreatic tumours producing insulin, gastrin, glucagon, and vasoactive intestinal peptide. Gel permeation chromatography of the IAPP-LI revealed that, except in the carcinoid, more than 80% coeluted with synthetic human IAPP. The remaining immunoreactivity consisted of variable amounts of larger and smaller molecular forms. The concentration of IAPP-LI in the circulation of patients with diagnosed pancreatic endocrine tumors was not significantly elevated above normal fasting levels. IAPP is, therefore, produced by a range of endocrine tumors and may relate to the deposition of endocrine amyloid.
 ...
PMID:Islet amyloid polypeptide-like immunoreactivity in human tissue and endocrine tumors. 847 84

Amylin is a normal secretory protein of the pancreatic beta-cells as well as a major constituent of the islet amyloid deposits in patients with non-insulin-dependent diabetes mellitus. We studied the effects of amylin on the release of insulin and glucagon from the isolated perfused rat pancreas. Rat amylin was dissolved in basal perfusates to a final concentration of 100 nM. Amylin did not alter glucose-stimulated secretion of insulin but significantly inhibited arginine-stimulated secretion of insulin (control: 20.9 +/- 1.4 pmol/min; amylin group: 14.8 +/- 1.6 pmol/min, p < 0.05). Amylin did not alter the release of glucagon from the perfused rat pancreas in response to 16.7 mM glucose and 10 mM arginine. These findings suggest that amylin may modulate the secretion of insulin from pancreatic beta-cells.
 ...
PMID:Effects of amylin on the release of insulin and glucagon from the perfused rat pancreas. 847 49

Islet amyloid polypeptide (IAPP) is the main constituent of pancreatic islet amyloid, observed in the pancreases from patients with Type 2 diabetes mellitus. IAPP is synthesized by the pancreatic beta-cells. In order to study the secretion characteristics of IAPP in Type 2 diabetes mellitus, plasma IAPP was measured during a provocation test with glucagon in 33 Type 2 diabetic patients and 18 non-diabetic subjects. The median fasting IAPP level was 5.7 (range 1.1-13.1) pmol l-1 in the 27 patients treated with oral hypoglycaemic agents and 2.7 (1.9-5.9) in the 6 patients on insulin. In the non-diabetic group fasting IAPP was 5.7 (2.2-10.1). Six minutes after glucagon administration median IAPP rose to 9.4 (1.7-31.0) and 6.1 (5.1-10.2) in the respective diabetic groups, and to 16.8 (4.0-41.0) in the non-diabetic subjects (p << 0.05). The correlation coefficient between change in IAPP and change in C-peptide was 0.68 in the diabetic group. We conclude that intravenous administration of glucagon stimulates IAPP release from the beta-cell. This provocation test is easy to perform and can be used on a large scale in the study of IAPP secretion in Type 2 diabetes mellitus.
 ...
PMID:Plasma concentrations of islet amyloid polypeptide after glucagon administration in type 2 diabetic patients and non-diabetic subjects. 850 14

Amylin is a recently discovered 37 amino acid peptide secreted into the bloodstream, along with insulin, from pancreatic beta-cells. It is about 50% identical to calcitonin gene-related peptides (CGRP alpha and CGRP beta) and structurally related to the calcitonins. Amylin can elicit the vasodilator effects of CGRP and the hypocalcaemic actions of calcitonin, while these peptides can mimic newly discovered actions of amylin on carbohydrate metabolism. The different relative potencies of these peptides suggest that they act with different selectivities at a family of receptors. Amylin is deficient in insulin-dependent diabetes mellitus, while plasma levels are elevated in insulin-resistant conditions such as obesity and impaired glucose tolerance. In this Viewpoint article, Tim Rink and colleagues propose that amylin is an endocrine partner to insulin and glucagon; deficiency or excess of amylin may therefore contribute to important metabolic diseases.
 ...
PMID:Structure and biology of amylin. 851 54

Several peptides have been proposed as regulators of nutrient release from the stomach and subsequent uptake from the gut. Using a phenol red gavage method, we compared the potencies of subcutaneously preinjected amylin, glucagon-like peptide-1 (7-36)amide (GLP-1), cholecystokinin octapeptide (CCK-8), gastric inhibitory peptide (GIP), glucagon, and pancreatic peptide on slowing the release of an acaloric gel from rat stomach. The latter three peptides did not fully inhibit gastric emptying at subcutaneous doses up to 100 micrograms. Amylin, GLP-1, and CCK-8 fully inhibited gastric emptying, with ED50s of 0.42 +/- 0.07, 6.1 +/- 0.12, and 8.5 +/- 0.20 nmol/kg +/- SE of log, respectively.
 ...
PMID:Dose-responses for the slowing of gastric emptying in a rodent model by glucagon-like peptide (7-36) NH2, amylin, cholecystokinin, and other possible regulators of nutrient uptake. 854 64

Many peptides have been shown to modulate nutrient intake. In most cases, these peptides decrease food intake, but in a few cases they have been demonstrated to stimulate feeding. Infusion of insulin peripherally will decrease food intake unless hypoglycemia occurs where the reduced glucose is a stimulus to feeding. Other pancreatic hormones including glucagon, amylin, pancreatic polypeptide, and enterostatin reduce food intake. Of the gastrointestinal hormones, cholecystokinin has been the most widely studied and reduces food intake in a number of species, including human beings. Gastrin-releasing peptide and its relative bombesin have been shown to decrease food intake in experimental animals and man. Somatostatin reduces food intake in experimental animals, but no clinical studies are available. Four pituitary peptides also modify food intake. Vasopressin decreases feeding. In contrast, injections of desacetyl melanocyte stimulating hormone (dMSH), growth hormone, and prolactin are associated with increased food intake. Finally, there are a group of miscellaneous peptides which modulate feeding. beta-casomorphin, a hepta peptide produced during the hydrolysis of casein, stimulates food intake in experimental animals. In contrast, the other peptides in this group including calcitonin, apolipoprotein A-IV, the cyclized form of histidyl-proline, several cytokines, and thyrotropin-releasing hormone decrease food intake. Many of these peptides act on gastrointestinal or hepatic receptors which relay messages to the brain via the afferent vagus nerve. As a group they provide a number of leads for potential drug development.
 ...
PMID:Nutrient intake is modulated by peripheral peptide administration. 869 60

Development of a high capacity multiplex reverse transcriptase-polymerase chain reaction protocol has allowed us to screen lineage related rat islet tumors classified as alpha-, beta-, and delta-like as judged by their hormone profile for differential expression of more than 50 selected genes. We find that in addition to insulin the insulinoma express the normal beta-cell markers Pdx-1, IAPP, and Glut-2, and that these markers are absent from the glucagonoma: a reflection of the normal alpha-cell. Furthermore, this study suggests that the GLP-1, glucagon, GIP, IGF-1, and insulin receptors as well as E-cadherin, R-cadherin, Id-1, and Id-2 are differentially expressed within the islet of Langerhans. Importantly, insulinoma-specific expression of the recently cloned homeodomain protein Nkx 6.1 predicted beta-cell-specific expression in the normal islet. Immunohistochemistry using antibodies raised against recombinant Nkx 6.1 did indeed localize Nkx 6.1 expression exclusively to the nuclei of normal islet beta-cells. Apart from pancreatic islets only the antral part of the stomach contained Nkx 6.1 mRNA. We conclude that multiplex reverse transcriptase-polymerase chain reaction-based mRNA profiling is a powerful tool to identify differentially expressed genes within phenotypically related cells and propose that Nkx 6.1 is involved in specifying the unique characteristics of the beta-cell.
 ...
PMID:mRNA profiling of rat islet tumors reveals nkx 6.1 as a beta-cell-specific homeodomain transcription factor. 870 31


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