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)

In vitro glucagon (1-100 microgram/ml) has been shown to inhibit the degradation of bradykinin by kininases present in kidney microsomes and erythrocytes. Glucagon was less active on kininases present in plasma and was inactive on purified pancreatic carboxypeptidase B. In conscious dogs the intravenous infusion of glucagon (10 microgram/min) increased urine flow (160%) and urine kinin excretion (130%) and decreased urine kallikrein excretion (14%). It is suggested that in vivo inhibition of kininases might contribute to the biological effects of glucagon.
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PMID:Kininase inhibition by glucagon. 58 Jan 44

Developmental patterns for rat pancreatic opioid peptides and islet hormones were studied from gestational day 20 through adulthood. Fetal tissue was obtained as well as pancreas at birth (day 0), and postnatal days 3, 7, 14, and 21, and 7 weeks. The hormones measured included insulin, glucagon, and somatostatin. The opioids measured were beta-endorphin, Met- and Leu-enkephalins, and the high molecular weight enkephalin precursors. Pancreata were pooled as necessary and extracted (acid alcohol, or hot acetic acid), and opioids were further purified on reversed-phase C-18 (Sep-pak) cartridges. In all instances measurements were made by radioimmunoassays. Precursor peptides were first digested (with trypsin and carboxypeptidase B) prior to immunoassay. All opioids and hormones except the precursors for enkephalins showed a well-defined surge in pancreatic concentration during the first postnatal week. In contrast, the precursors had the highest concentration in the fetus, and by the seventh day of life had decreased by greater than 50%. This progressive decrease may represent maturation of the enkephalin convertase and trypsin-like enzymes in the islets. The opioid and hormonal surges that we have described are similar to the surge in islet concentration of thyroid-releasing hormone (TRH) previously described in neonatal rat islets. It is suggested that these postnatal alterations in opioid and hormone concentration relate to a specific function in the development of the endocrine pancreas.
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PMID:Developmental patterns for pancreatic opioids in the rat. 253 May 76

Enkephalin convertase (carboxypeptidase E,H; EC 3.4.17.10) is a carboxypeptidase B-like enzyme which appears to be physiologically associated with the biosynthesis of the enkephalins and certain other peptides. We have localized enkephalin convertase in the brain and other tissues autoradiographically by labeling studies with [3H]guanidinoethylmercaptosuccinic acid ([3H]GEMSA). In the brain, [3H]GEMSA localizations parallel enkephalin distribution but with certain exceptions, suggesting a role in relation to other peptides. In the pancreas, [3H]GEMSA binding sites are localized to the islets suggesting an involvement in insulin, glucagon, or somatostatin formation. The selective concentration of [3H]GEMSA grains in cardiac atria suggests a link to atrial natriuretic factor.
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PMID:Enkephalin convertase: characterization and localization using [3H]guanidinoethylmercaptosuccinic acid. 313 43

Uraemia was induced in pigs by ligation of the renal vascular pedicle, and uraemic plasma was analysed for glucagon and glucagon-related peptides. A preponderance of large molecular weight (Mr) components comprising glicentin and moieties of slightly lower Mr was found, accounting for 73 +/- 3% (mean +/- SEM, n = 12) of the total plasma glucagon-like immunoreactivity. Comparisons with glicentin 1-61, produced by controlled, stepwise, consecutive digestion of purified natural glicentin with carboxypeptidases (carboxypeptidase A followed by carboxypeptidase B, and again by carboxypeptidase A and B), gel filtration, ion exchange chromatography, reverse phase HPLC and radioimmunoassays for the glucagon sequences 6-15 and 19-29 and for the glicentin sequence 12-30 all indicate that glicentin 1-61 constitutes approximately 57% of the large Mr glucagon-related peptides found in uraemia in pigs.
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PMID:Glicentin 1-61 probably represents a major fraction of glucagon-related peptides in plasma of anaesthetized uraemic pigs. 374 26

Many small biologicaly active peptides are derived from larger precursor forms which fulfil a variety of roles in the synthesis, segregation and intracellular migration of secretory products. Limited proteolysis may occur at several stages during this process, giving rise to products that are either degraded (e.g. the prepeptides) or discharged coordinately from their cells of origin during exocytosis (e.g. insulin and C-peptide). Molecular defects have recently been found to occur at cleavage sites in proinsulin as well as in other proproteins, and these point mutations may, in some instances, be responsible for familial metabolic disorders. The nature and cell specificity of the proteolytic enzymes involved in the conversion of the various precursor forms remains unresolved. Recent studies in our laboratory have led to the identification of precursors of glucagon and somatostatin in rat islets of Langerhans. Analysis of tryptic maps of these precursors has shown that a trypsin-like enzyme would be sufficient to cleave the C-terminally located somatostatin sequence from its precursor (relative molecular mass 12,500), but that both trypsin-like and carboxypeptidase B-like enzymes would be necessary to cleave the internal glucagon sequence from its prohormone (relative molecular mass 18,000). Molecular cloning techniques have provided valuable new approaches to analysing the structures of a variety of precursor forms, including those for insulin, gastrin, growth hormone, adrenocorticotropic hormone and the endorphins, and in the future will undoubtedly shed more light on the structures of their chromosomal genes, the mechanisms regulating their expression, and their evolutionary origins.
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PMID:Formation of biologically active peptides. 610 30

The biosynthesis of insulin, in particular the occurrence of a proinsulin-like molecule (PILM), in the pancreas of the green anole, Anolis carolinensis, was investigated. The laboratory rat was used for comparison and validation of the procedures. Anolian pancreases were incubated in vitro with radiolabeled leucine or proline. Radioactivity incorporated into the acidic ethanol-soluble (AES) phase increased in an essentially linear manner with time. Selective incorporation of labeled amino acids into AES material was not enhanced by a high concentration of glucose (6 mg/ml), by the addition of glucagon, which increases cyclic AMP levels, or by the addition of cytochalasin B; yet all three conditions result in stimulated insulin secretion. Gel filtration of the AES material on columns of Bio-Gel P-30 revealed a major peak of radioactivity whose apex followed closely the apogee of porcine proinsulin. When this presumptive PILM was treated with trypsin and carboxypeptidase B, the radioactivity was shifted towards later elution volumes, but the peak of the converted anolian material was not coincidental with marker insulin. Immunopurification techniques and additional molecular filtrations resulted in the isolation of fractions with both insulin-like immunoreactivity (IRI) and radioactivity derived from tritium-labeled leucine. One peak of radiolabel was present in the region of the proinsulin standards. The level of radioactivity in the region of the insulin standards was relatively high after two days of organ culture of splenic pancreases. By polyacrylamide gel electrophoresis proteins that incorporated radiolabeled amino acids and had insulin-like immunoreactivity possessed migration patterns similar to those of mammalian proinsulin and insulin. The insulin-like component was less readily demonstrated than the proinsulin-like component and raises the possibility that anolian PILM may be a major storage form in this species. The results are consistent with the synthesis of a proinsulin-like precursor in the beta cells of the green anole. The results also provide evidence for a precursor-product relationship in the anolian beta cell.
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PMID:Biosynthesis of a proinsulin-like molecule in the pancreas of a lizard. 635 1

Glicentin (a highly purified 100-amino acid peptide with glucagon-like immunoreactivity from porcine gut) was subjected to limited digestion with trypsin and carboxypeptidase B, and the resulting peptides were studied by gel filtration and region-specific glucagon radioimmunoassays. Similar digests of glucagon and purified fragments of glucagon were studied in parallel. Glicentin gave rise to peptides that corresponded closely to the 1-17 and 19-29 fragments of glucagon. Also, 125I-labelled glicentin and 125I-labelled glucagon gave rise to identical fragments after trypsin treatment. On the basis of this and other evidence [Jacobsen, Demandt, Moody & Sundby (1977) Biochim. Biophys. Acta 493, 452-459] it is concluded that glicentin contains the entire glucagon sequence at residues number 64-92 and thus fulfills one of the requirements for being a 'proglucagon'.
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PMID:Evidence that glicentin contains the entire sequence of glucagon. 689 48

Immunochemical and immunocytochemical techniques have been used to identify and characterize glucagon-related peptides of the rat central nervous system. These peptides show immunoreactivity with antiglucagon sera directed towards the central portion of the hormone, but not with antisera specific for the free COOH terminus of glucagon. Highest concentrations were found in hypothalamus (6.1 +/- 1.6 ng/g wet weight) although lower amounts (approximately 2 ng/g) were found in cortex, thalamus, cerebellum, and brain stem. Gel filtration of brain extracts revealed at least two immunoreactive forms, which have molecular weights of about 12,000 and 8000. Both peptides had radioimmunoassay dilution curves parallel to the curve for glucagon and both had identical counterparts in extracts of rat intestine. Digestion of the brain and intestinal peptides with trypsin plus carboxypeptidase B released the immunoreactive COOH-terminal tryptic fragment of pancreatic glucagon from these larger forms. Immunocytochemical studies using antiglucagon serum and peroxidase-antiperoxidase staining identified glucagon-like material in neuronal cell bodie and processes in the magnocellular portion of the paraventricular nucleus, as well as in scattered cells in the supraoptic nucleus and in fibers in the median eminence. These results suggest that glucagon-containing peptides that have undergone the intestinal type of posttranslational modification are present in neuronal cells of the rat hypothalamus.
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PMID:Identification and localization of glucagon-related peptides in rat brain. 693 48

Exposure of sections of ileal mucosa to enzymatic digestion with trypsin and carboxypeptidase B reveals a population of immunofluorescent cells after incubation with a specific C-terminally directed antiglucagon serum. These cells, unreactive before enzyme treatment, were identified as L-cells by their immunoreactivity to antiglicentin serum and to cross-reacting (N-terminal) antiglucagon sera. The presence in the L-cells of antigenic sites characteristic of the glucagon-containing cells (A-cells) emphasizes the close relationships between these two cell types, and it further supports the hypothesis of glicentin as a glucagon precursor.
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PMID:Transformation of glicentin-containing L-cells into glucagon-containing cells by enzymatic digestion. 698 2

Under specific pathogen-free conditions, 1.3% to 1.8% of litters born in our inbred 101/H and C3HeB/FeJ mouse colonies had pups with steatorrhea and runting. Clinically affected male and female pups were first identified when they were from 14 to 25 d old. Unaffected littermates were healthy and were weaned successfully. Postmortem findings in 8 clinically affected mice included a small, poorly differentiated exocrine pancreas comprising cytokeratin-negative duct-like structures but lacking recognizable acinar cells with their normal carboxypeptidase B-positive zymogen granules. Endocrine pancreas islets were unremarkable and contained insulin-positive beta cells and glucagon-positive alpha cells. There was mild inflammation of the hindgut but no evidence of intestinal pathogens or marked inflammation or necrosis of pancreas, either alone or as part of a multisystemic inflammatory condition. Sera from pups in 4 affected litters did not contain antibodies to reovirus 3, mouse coronavirus, rotavirus, or mouse adenovirus 2. Furthermore, 4 sets of parental mice and sentinel mice from the facility were negative for 13 viruses, bacteria, and parasites. C3HeB/FeJ and 101/H inbred strains may be genetically predisposed because the steatorrhea and runting was absent in 13 other mouse strains and subspecies bred in the specific pathogen-free facility. This condition resembles exocrine pancreas hypoplasia, but the inheritance is complex. A wider implication is that runting coupled with steatorrhea are phenotypic criteria to suspect pancreatic disease that could be used in the context of a mouse N-ethyl-N-nitrosourea-mutagenesis program to identify potential mutants with defects in pancreas development.
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PMID:Spontaneous exocrine pancreas hypoplasia in specific pathogen-free C3HeB/FeJ and 101/H mouse pups causes steatorrhea and runting. 1753 23


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