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)

Aerolysin, a cytolytic bacterial exotoxin, was radioiodinated by using the Iodogen reagent. Binding of the labeled toxin to rat erythrocytes was inhibited by the native protein and by anti-aerolysin antibody. Toxin, once bound, was not removed by the addition of a large excess of free aerolysin. Binding of the radioactive toxin to erythrocytes of different species paralleled the hemolytic specificity of the unlabeled toxin. Pretreatment of the rat erythrocytes with trypsin, which removed a major membrane glycoprotein, resulted in a dramatic decrease in binding, whereas chymotrypsin treatment had no effect. Binding was inhibited by a glycoprotein fraction isolated from these cells but not by a total rat erythrocyte glycolipid preparation. Aerolysin caused the formation of holes in erythrocytes which were sized by measuring the release of labeled molecular weight markers. Glucagon (molecular weight 3550) and smaller molecules entrapped in human or rat erythrocytes were released by treatment with aerolysin, whereas methoxyinulin (molecular weight 5500) and larger molecules were not. Aerolysin also caused the release of glucose from large unilamellar lipid vesicles. The results indicate that a specific glycoprotein receptor facilitates the interaction of aerolysin with erythrocyte membranes. Binding is followed by the formation of discrete holes or pores, and this results in cell rupture by a colloid-osmotic process.
 ...
PMID:Membrane glycoprotein receptor and hole-forming properties of a cytolytic protein toxin. 708 38

The transport of human alpha 1-acid glycoprotein from the circulation to the bile has been studied in the rat. Biliary excretion was proportional to the i.v. injected dose, and the percentage excreted remained constant. The amount excreted in the bile (over 4 hr) was inversely related to the rate of hepatic (hepatocyte) uptake and the galactose receptor which is specific for asialo glycoproteins was not involved. Reinjection of the glycoprotein excreted in bile resulted in a similar proportion of the dose being reexcreted, suggesting that a subset of the glycoprotein is not selected for excretion in bile. Transit times from blood to bile for glucagon, insulin, alpha 1-acid glycoprotein, fetuin, albumin, and carcinoembryonic antigen were directly related to their molecular weights. Removal of sialic acid from the asialo glycoproteins did not affect these transit times. Possible mechanisms for the biliary excretion of alpha 1-acid glycoprotein are discussed.
 ...
PMID:The mechanism of biliary excretion of alpha 1-acid glycoprotein in the rat: evidence for a molecular weight-dependent, nonreceptor-mediated pathway. 714 91

After trauma or sepsis, the liver undergoes a reprioritization of export protein synthesis with elevated production of some acute-phase reactants and reduced production of others. We have examined the effects of combinations of insulin and the counterregulatory hormones (dexamethasone, glucagon, and epinephrine), in the presence or absence of interleukin (IL)-6, on the production by isolated hepatocytes of the positive acute-phase proteins C-reactive protein, alpha 1-antichymotrypsin, alpha 1-acid glycoprotein, and haptoglobin, and the negative acute-phase proteins prealbumin and transferrin. The effect of IL-6 on the production of the above proteins was influenced significantly by insulin and all of the counterregulatory hormones. Significant three-way interactions as well as higher order interactions between the stress hormones and insulin were seen in the case of C-reactive protein. The results indicate that both positive and negative acute-phase proteins respond differently to insulin and the counterregulatory hormones and that the potential exists for the regulation of synthesis of individual acute-phase reactants by interaction between the cytokine network and the classical endocrine hormones.
 ...
PMID:Insulin and counterregulatory hormones influence acute-phase protein production in human hepatocytes. 754 33

The carbohydrate-deficient glycoprotein (CDG) syndrome type 1 is a genetic multisystem disorder, characterized by hypoglycosylation of glycoproteins and presenting with neurologic impairment. In 12 girls and 14 boys, we confirmed the diagnosis of CDG syndrome type 1 by immune-isoelectric focusing of serum sialotransferrins, and we examined the endocrine status singly or sequentially, including a 16-y follow-up of the index cases, a pair of monozygotic girls. Serum FSH levels were normal in newborns and prepubertal children, but elevated in female toddlers and teenagers, as well as in adolescent males. Serum LH concentrations displayed an analogous age-dependent pattern. In adolescent girls, serum estradiol remained low. FSH bioactivity was low normal, as was the bioactive/immunoreactive FSH ratio. However, exogenous gonadotropins evoked an estradiol response and induced ovarian follicular growth. Male patients virilized at puberty; however, testicular volume was subnormal. The thyroid axis was hallmarked by thyroid-binding globin deficiency and, during infancy, increased serum TSH concentrations. A subgroup of female patients presented hypersomatotropism and/or hyperprolactinemia. During adolescence, the index cases responded to glucagon with normal glycemic, but exaggerated insulin and paradoxically augmented growth hormone responses. The hypothalamo-pituitary area appeared intact on magnetic resonance imaging. Circulating IGF-1 levels were in the lower normal range and transcortin concentrations decreased. In conclusion, a study of endocrine aspects of a major glycosylation disorder revealed an age-dependent constellation, including hypergonadotropic hypogonadism with deficient FSH rather than LH action; transient hyperthyrotropinemia; inconsistent hyperprolactinemia; hyperglycemia-induced growth hormone release; deficiencies of hormone-binding glycoproteins and possibly decreased insulin sensitivity, thus pointing to the importance of glycoprotein glycosylation for pediatric endocrinology.
 ...
PMID:Endocrinology of the carbohydrate-deficient glycoprotein syndrome type 1 from birth through adolescence. 759 77

The mRNA for a glucagon receptor is present in five glucagon-responsive tissues of rat, including the liver, heart, pancreatic islets, kidneys and adipose tissue. The mature mRNA of this receptor is likely to derive from one gene only in all tissues investigated. The maturation of the pre-mRNA requires the splicing of 11 introns. This proceeds stepwise at the 5' end but a single intronless ORF is finally operative. The receptor is a glycoprotein endowed with 485 amino acids (including the signal peptide).
 ...
PMID:[Molecular cloning and functional expression of glucagon receptors in the liver, the heart and various other tissues]. 779 50

We report the histological, immunohistochemical and ultrastructural changes in mice containing a chimeric glucagon-simian virus 40 T antigen (SV40Tag) gene. Transgene expression was detected in endocrine cells of pancreas, small and large intestine. Hyperplasia of glucagon-containing cells developed in pancreas and large bowel by gestational day 19. In large bowel, hyperplastic cells increased in number postnatally and invasive carcinomas were identified at 4 weeks; several animals had lymph node metastases. In contrast, no pathology was detected in the small bowel in any of the transgenic mice. Colonic tumours expressed SV40Tag, proglucagon-derived peptides and peptide YY (PYY); scattered cells contained cholecystokinin or glycoprotein hormone alpha-subunit. Somatostatin or serotonin was also detected in some tumours. By electron microscopy, the colonic tumours retained features of endocrine differentiation, but secretory granules were smaller than those of non-tumorous intestinal glucagon-producing L cells. In postnatal pancreas, atypical cells containing SV40Tag and glucagon were initially clustered at the periphery of islets; this atypical hyperplasia progressed to neoplasia by 11-12 weeks. Some neoplastic pancreatic cells contained glucagon, PYY or vasoactive intestinal peptide immunopositivity, but most were negative for all peptides; they contained immunoreactivity for tyrosine hydroxylase and by electron microscopy, pancreatic tumour cells had neuronal features. Pancreatic polypeptide was not detected in the non-tumorous islets of transgenic animals. This line of transgenic mice provides a model for the analysis of endocrine tumour progression in the gut and pancreas.
 ...
PMID:Development of colonic and pancreatic endocrine tumours in mice expressing a glucagon-SV40 T antigen transgene. 860 71

Isolation and structural characterization of the rat corticotropin releasing factor receptor (CRFR) gene was performed to determine the exon/intron organization of the coding region and the potential for splice variants. The CRFR gene contains 13 exons and 12 introns, and the positions of the exon/intron junctions are similar to those of other Class II G protein-coupled receptor genes including the parathyroid hormone and glucagon receptors. The promoter resides within 593 base pairs of the initiation codon and the major transcriptional start site at nucleotide -238. This domain does not possess a TATA box but contains multiple Sp1 and AP-2 sites upstream and downstream of the major transcriptional start site. Intron junctions were identified in the extracellular, transmembrane (TM), and cytoplasmic (C) domains of the CRFR, giving the potential for differential signal transduction by splice variants. CRFR cDNAs derived from rat Leydig cell mRNA included the pituitary Form A, which spans exons 1-13, and two splice variants with deletion of exon 3 or exons 7, 11, and 12. An evolutionary link between the intronless TM/C module of the glycoprotein hormone receptors and the intron-containing TM/C module of the CRFR is suggested by the common position of the luteinizing hormone receptor Form D alternate acceptor splice site and the CRFR intron 12.
 ...
PMID:The genomic structure of the rat corticotropin releasing factor receptor. A member of the class II G protein-coupled receptors. 866 41

Pancreastatin is a 49 amino acid peptide first isolated, purified and characterized from the porcine pancreas, and whose biological activity in different tissues can be assigned to the C-terminal part of the molecule. Pancreastatin has a prohormonal precursor, chromogranin A (CGA), which is a glycoprotein present in neuroendocrine cells, including the endocrine pancreas. Both intracellular and extracellular processing of CGA can yield pancreastatin. This processing is tissue-specific, with the pancreatic islet and antral gastric endocrine cells being the major source of fully processed pancreastatin. Most of the circulating CGA is secreted by chromaffin tissue. Therefore, peripheral processing of CGA is probably the major indirect source of pancreastatin. Pancreastatin seems to have a general modulatory control on endocrine (insulin, glucagon, parathormone) and exocrine (pancreatic, gastric) secretion from tissues close to the source of production. This has led to the assumption that pancreastatin may be a peptide with an autocrine and paracrine function. It has recently been revealed to be a peptide with a metabolic function counter-regulatory to insulin action. This effect, in conjunction with the inhibitory effect on insulin and pancreatic exocrine secretion, points to a role in the physiology of stress. The molecular mechanism of the glycogenolytic effect of pancreastatin is better known, although further work is still needed. In general, more studies should be carried out at the molecular level to investigate the mechanism of action of pancreastatin and thus to clarify its physiological role in the neuroendocrine system.
 ...
PMID:Pancreastatin: further evidence for its consideration as a regulatory peptide. 867 28

Due to the increased costs of medical care, a cost-benefit analysis is needed when trying for the 'ultimate' biochemical diagnosis of gastro-enteropancreatic (GEP) tumours. The glycoprotein chromogranin family has proved useful in screening for neuroendocrine tumours. In patients with midgut carcinoid tumours, chromogranin A is more sensitive than urinary 5-hydroxyindoleacetic acid but by combining these two biochemical markers most GEP tumours can be diagnosed. Chromogranin A is also a prognostic marker for survival in patients with midgut carcinoid tumours. Pancreastatin constitutes a part of the chromogranin A molecule and is a less sensitive general screening marker for neuroendocrine gut and pancreatic tumours, but levels, in combination with chromogranin A, might give some insight into tumour biology. Specific markers such as gastrin, glucagon, vasoactive intestinal peptide, insulin, neuropeptide K and substance P should be used to further characterise hormone production in neuroendocrine tumours. However, in some patients, confirmation of diagnosis requires provocation tests, such as the secretin or meal provocation tests. Staging information can be obtained by new investigations such as intra-operative or endoscopic ultrasound, octreoscan, and positron emission tomography. We combine the biochemical characterisation of neuroendocrine tumours with studies of growth factors/receptors, adhesion molecules, proliferation markers, somatostatin receptor content, induction of the enzymes p68 kinase and 2'5'-A-synthetase, and apoptosis, to establish a sound rationale for therapeutic decisions, enabling every patient to receive individualised treatment.
 ...
PMID:The ultimate biochemical diagnosis of gastro-enteropancreatic tumours. 881 68

Fetal antigen 1 (FA1) is a glycoprotein containing six epidermal growth factor (EGF)-like repeats. It is closely similar to the protein translated from the human delta-like (dlk) cDNA and probably constitutes a proteolytically processed form of dlk. dlk is homologous to the Drosophila homeotic proteins delta and notch and to the murine preadipocyte differentiation factor Pref-1. These proteins participate in determining cell fate choices during differentiation. We now report that FA1 immunoreactivity is present in a number of neuroectodermally derived tumours as well as in pancreatic endocrine tumours. A negative correlation between FA1 and glucagon immunoreactants in these tumours prompted a reexamination of FA1 immunoreactants during fetal pancreatic development. At the earliest stages of development, FA1 was expressed by most of the non-endocrine parenchymal cells and, with ensuing development, gradually disappeared from these cells and became restricted to insulin-producing beta cells. Throughout development FA1 was not detected in endocrine glucagon, somatostatin or pancreatic polypeptide cells. Moreover, developing insulin cells that coexpressed glucagon were negative for FA1. Thus, there was a negative correlation between FA1 and glucagon both in tumours and during development. These results, together with FA1/dlk's similarity with homeotic proteins, point to a role of FA1 in islet cell differentiation.
 ...
PMID:FA1 immunoreactivity in endocrine tumours and during development of the human fetal pancreas; negative correlation with glucagon expression. 898 41


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