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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 7- to 10-fold increase in the rat liver serine:pyruvate aminotransferase activity after glucagon administration was shown to occur mainly in the mitochondrial matrix of parenchymal cells. The enzyme was purified from glucagon-treated rat liver mitochondria to apparent homogeneity as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A specific rabbit antibody was prepared against the purified enzyme. Upon Ouchterlony double diffusion analysis, the mitochondrial extracts of glucagon-treated rat liver produced a single and fused precipitin line between the purified enzyme against the antibody. The supernatant fraction of glucagon-treated rat liver and the mitochondrial extracts of normal liver were also shown to make a single and fused precipitin line with the purified enzyme, when applied in large quantities. The quantitative immunotitration demonstrated that the glucagon-induced increase in the activity of liver serine:pyruvate aminotransferase were accompanied by the parallel increase in the amount of the enzyme antigen. Isotopic leucine incorporation studies showed that the relative rate of synthesis of the enzyme was increased approximately 10-fold by glucagon administration under the conditions employed. The rate of the degradation of the aminotransferase in the normal rat liver was a relatively slow process with a half-life of approximately 30 h. Thus the accumulation of serine:pyruvate aminotransferase in rat liver mitochondria by glucagon treatment can be ascribed mainly to the rise in the rate of enzyme synthesis.
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PMID:Immunochemical studies on induction of rat liver mitochondrial serine: pyruvate aminotransferase by glucagon. 41 59

1. The local anaesthetic benzyl alcohol progressively activated glucagon-stimulated adenylate cyclase activity up to a maximum at 50 mM-benzyl alcohol. Further increases in benzyl alcohol concentration inhibited the activity. The fluoride-stimulated adenylate cyclase activity was similarly affected except for an inhibition of activity occurring at low benzyl alcohol concentrations (approx. 10 mM. 2. The fluoride-stimulated adenylate cyclase activity of a solubilized enzyme preparation was unaffected by any of the benzyl alcohol concentrations tested. 3. Increases in 3-phenylpropan-1-ol and 5-phenylpentan-1-ol concentrations progressively activated both the fluoride- and glucagon-stimulated adenylate cyclase activities up to a maximum, above which further increases in alcohol concentration inhibited the activities. 4. The 'break' points in Arrhenius plots of glucagon-stimulated adenylate cyclase activity in native plasma membranes, and in plasma membranes fused with synthetic dimyristoyl phosphatidylcholine so as to constitute 60% of the total lipid pool, were decreased by approx. 6 degrees C by addition of 40 mM-benzyl alcohol. This was accompanied by a fall in the associated activation energies. 6. Arrhenius plots of fluoride-stimulated adenylate cyclase activity in the presence and absence of 40 mM-benzyl alcohol were linear, although addition of benzyl alcohol caused a dramatic decrease in the associated activation energy of the reaction. 7. 5'-Nucleotidase activity was stimulated by benzyl alcohol, and the 'break' point in the Arrhenius plot of its activity was decreased by about 6 degrees C by addition of 40 mM-benzyl alcohol to the assay. 8. It is suggested that benzyl alcohol effects a fluidization of the bilayer, which is clearly demonstrated by its ability to lower the temperature of a lipid phase separation occurring at 28 degrees C in the outer half of the bilayer to around 22 degrees C. The increase in bilayer fluidity relieves a physical constraint on the membrane-bound adenylate cyclase, activating the enzyme. 9. The various inhibition phenomena are discussed in detail, together with the suggestion that the interaction between the uncoupled catalytic unit of adenylate cyclase and the lipids of the bilayer is altered on its physical coupling to the glucagon receptor.
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PMID:The activity of glucagon-stimulated adenylate cyclase from rat liver plasma membranes is modulated by the fluidity of its lipid environment. 69 51

Transcription of the rat serine dehydratase (SDH) gene is induced by glucagon, mediated by the action of cAMP. To identify the nucleotide sequences in the SDH gene responsible for this regulation, we constructed chimeric genes containing different portions of the 5' flanking region of the rat SDH gene fused to the structural sequence encoding the bacterial reporter enzyme, chloramphenicol acetyltransferase (CAT). The transcriptional activities of the fusion genes introduced into the rat hepatoma cell line 7AD-7 were assayed by measuring CAT activity in the cell lysates. Chlorophenylthio-cyclic AMP (CPT-cAMP), a potent protein kinase A activating agent, stimulated the expression of SDH-CAT fusion genes, and these inductions could be enhanced further by the addition of dexamethasone, although the glucocorticoid alone had no effect on CAT activity. Deletion analysis demonstrated that an 80 bp region located approximately 3.5 kb upstream from the transcription initiation site of the rat SDH gene was responsible for stimulation of transcription by CPT-cAMP, whereas the 120 bp region immediately upstream of the cAMP responsive element (CRE)-containing sequences is essential for the enhancement of CPT-cAMP induction by the glucocorticoid.
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PMID:Identification of regions in the rat serine dehydratase gene responsible for regulation by cyclic AMP alone and in the presence of glucocorticoids. 133 28

The rat glucagon gene 5'-flanking region contains a pancreatic islet-specific enhancer-like element, G3. It has been shown previously that G3-binding and transactivating proteins are present in islet cell lines expressing the glucagon, somatostatin, and insulin genes, but not in several nonislet cell lines. The present study now shows that the glucagon G3 transcription factor binds to DNA sequences within cis-acting elements of the rat somatostatin and rat insulin-I genes that have been defined by others as pancreatic islet-specific transcriptional enhancers. In addition, when fused to glucagon or somatostatin minimal promoters in reporter plasmids, these enhancer elements of the three islet hormone-producing genes functionally activate transcription when transfected into islet cell lines producing glucagon, insulin, or somatostatin. The enhancer elements of the three different islet polypeptide hormone genes define a potential consensus motif that binds islet cell type-specific transcription factors.
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PMID:The pancreatic islet-specific glucagon G3 transcription factors recognize control elements in the rat somatostatin and insulin-I genes. 168 54

Tumor-infiltrating lymphocytes were isolated from a primitive neuroectodermal tumor and fused with GM4672 cells, resulting in hybrids secreting human IgM-kappa antibody, which is reactive to olfactory neuroblastoma tumor cells. Hybridoma clones 4F and 9G produce human monoclonal antibodies reactive to autologous and allogeneic neuroblastoma tumor cells and subsets of pancreatic islet cells in formalin-fixed tissues. They react specifically with dense core granules of glucagon and insulin-producing islet cells, but not with those in cells producing somatostatin. Calcitonin granules are not recognized by these antibodies. The area of localization of the granules is distinct from the component labeled by murine monoclonal antibodies to chromogranin A. The clones have remained stable in culture for over two years and continue to secrete up to 60 micrograms/mL of human IgM. This study demonstrates the possibility of directly analyzing the antibody repertoire of tumor-infiltrating B cells, and this technique may allow the development of human monoclonal antibodies to other novel cellular antigens.
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PMID:Human monoclonal antibodies to neuroendocrine granules derived from tumor-infiltrating lymphocytes isolated from a primitive neuroectodermal tumor. 196 74

Pyruvate kinase is a major regulatory enzyme of glycolysis. Transcription of the L-type pyruvate kinase (L-PK) gene in rat liver is induced by feeding a carbohydrate-rich diet. To investigate the regulatory DNA sequences required for this response, primary hepatocytes were transfected with plasmids containing the 5'-flanking sequence of the rat L-PK gene fused to the chloramphenicol acetyltransferase (CAT) gene. Sequences from -4300 to +12 of the L-PK gene directed an increase in CAT activity when hepatocytes were switched from media containing 10 mM lactate to 25 mM glucose. Average induction was 17-fold (n = 13; S.E. = 2.9). Addition of fructose to the media also induced CAT activity. Carbohydrate regulation of the L-PK promoter was retained with 5'-deletions to -197, but constructs deleted to -96 were completely unresponsive. The 101-base pair fragment from -197 to -96 of the L-PK gene can confer carbohydrate regulation when fused in either orientation to the heterologous thymidine kinase promoter, thus defining a carbohydrate response element in this region. Expression of the transfected gene was regulated by insulin and glucagon in a pattern similar to that seen for the endogenous L-PK gene, suggesting that control of L-PK promoter activity was responsible for carbohydrate-mediated changes in L-PK mRNA production.
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PMID:Localization of the carbohydrate response element of the rat L-type pyruvate kinase gene. 202 84

A pancreatic alpha-like cell line has been established from a glucagonoma arising in transgenic mice expressing a hybrid gene consisting of the rat glucagon-promoter sequence fused to the sequence encoding the SV40 T-antigen oncoprotein. The alpha-tumor cell 1 (alpha TC1) line maintained many characteristics of differentiated alpha-cells for greater than 40 passages in culture and expressed levels of glucagon mRNA 5- to 10-fold higher than those reported previously in rat and hamster islet cell lines. By radioimmunoassay, the cells synthesized considerable amounts of glucagon, glucagonlike peptide I (GLP-I), the major proglucagon fragment, and small amounts of unprocessed proglucagon but no free GLP-II. This distribution of peptides is similar to that found in extracts of rodent pancreases and is distinct from that seen with other islet cell lines, which process proglucagon in patterns more characteristic of intestinal cells. The GLP-I peptide in the alpha TC1 cell line was in the form of GLP-I-(1-37), which is inactive as a stimulator of insulin secretion, and not GLP-I-7-37) or -(7-36)-amide peptides, both of which are potent insulin secretagogues. The alpha TC1 cell line produced glucagon-related peptides in a relatively uniform pattern by immunocytochemistry, and electron microscopy revealed typical alpha-type (glucagon) secretory granules. Although the cell line was derived from an islet tumor producing only glucagon, the alpha TC1 cell line also produced insulin in addition to the glucagon peptides.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Proglucagon processing similar to normal islets in pancreatic alpha-like cell line derived from transgenic mouse tumor. 215 40

125I-Glucagon binding to rat liver plasma membranes was composed of high- and low-affinity components. N-Ethylmaleimide (NEM) and several other alkylating agents induced a dose-dependent loss of high-affinity sites. This diminished the apparent affinity of glucagon receptors for hormone without decreasing the binding capacity of membranes. Solubilized hormone-receptor complexes were fractionated as high molecular weight (Kav = 0.16) and low molecular weight (Kav = 0.46) species by gel filtration chromatography; NEM or guanosine 5'-triphosphate (GTP) diminished the fraction of high molecular weight complexes, suggesting that NEM uncouples glucagon receptor-N-protein complexes. Exposure of intact hepatocytes to the impermeable alkylating reagent p-(chloromercuri)benzenesulfonic acid failed to diminish the affinity of glucagon receptors on subsequently isolated plasma membranes, indicating that the thiol that affects receptor affinity is on the cytoplasmic side of the membrane. Hormone binding to plasma membranes was altered by NEM even after receptors were uncoupled from N proteins by GTP. These data suggest that a sensitive thiol group that affects hormone binding resides in the glucagon receptor, which may be a transmembrane protein. Alkylated membranes were fused with wild-type or cyc- S49 lymphoma cells to determine how alkylation affects the various components of the glucagon-adenylyl cyclase system. Stimulation of adenylyl cyclase with fluoride, guanylyl 5'-imidodiphosphate, glucagon, or isoproterenol was observed after fusion of cyc- S49 cells [which lack the stimulatory, guanine nucleotide binding, regulatory protein of adenylyl cyclase (Ns)] with liver membranes alkylated with 1.5 mM NEM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:N-ethylmaleimide uncouples the glucagon receptor from the regulatory component of adenylyl cyclase. 302 2

Glucagon, a peptide hormone which regulates hepatic carbohydrate metabolism, is processed from a larger precursor, proglucagon. The gene encoding proglucagon is expressed at high levels in the A cells of the pancreatic islets and the L cells of the intestine, indicating that specific factors present in these two phenotypically distinct cells direct cell-specific expression. To characterize the factors that mediate glucagon gene transcription, we analyzed the 5'-flanking region of the rat glucagon gene for the existence of cis-acting sequences that promote glucagon gene transcription. A series of fusion genes containing sequentially shortened 5'-flanking sequences of the rat glucagon gene were constructed and fused to the coding sequence of the reporter enzyme chloramphenicol acetyltransferase. Analyses of the transcription of these fusion genes after their transfection into choriocarcinoma cells, fibroblasts, and islet cell lines of different phenotypes indicate that cis-acting DNA elements promote glucagon gene transcription only in islet cell lines. Transcriptional activity was much higher in glucagon compared to insulin-producing islet cell lines with fusion genes containing 249 or more base pairs of glucagon 5'-flanking sequence. Deletion of DNA sequences upstream of -168 abolished the preferential expression in glucagon-producing cell lines, however glucagon-chloramphenicol acetyltransferase fusion genes containing 168 base pairs or more of 5'-flanking sequence remained transcriptionally active, but only in islet cell lines. Fusion genes containing 115 base pairs of glucagon gene 5'-flanking sequences were transcriptionally inactive. These studies indicate that cis-acting DNA sequences present in the 5'-flanking region of the rat glucagon gene mediate islet cell-specific gene transcription.
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PMID:Glucagon gene 5'-flanking sequences promote islet cell-specific gene transcription. 331 2

Islets of Langerhans in sections from the tail of the pancreas of corpulent LA/N-cp rats and lean controls aged 1, 3, 6 and 9 mo were examined by immunocytochemistry and morphometrically using an automatic image analyzer. The corpulent rats had significantly greater islet volumes at all ages, although islet hypertrophy tended to plateau after 6 mo. By 12 mo age the architecture of the islets was disrupted with large islets fused and showing areas of fibrosis and deposits of hemosiderin. The volume density (v/v, %) of islets in the parenchyma was significantly increased at each age step in corpulent rats reaching over 20% at 9 mo, and was greater in corpulent than in lean rats at all ages. In the corpulent rats, B-cell volume density dramatically with age and at all ages was significantly greater in corpulent than in lean rats. A-cell volume density was significantly greater in the corpulent rats than in lean rats at 1 and 9 mo. The mean B:A cell ratio was greater in corpulent than in lean rats at 3, 6 and 9 mo. There were more D cells per islet in corpulent than in lean rats up to 9 mo. These changes in cell populations were paralleled by qualitative changes in islet morphology and cellular topography such as increasingly irregular islet shape in corpulent animals and by variations in plasma levels of insulin and glucagon. In this strain of rats, obesity is associated with major changes in pancreatic morphology and this correlates strongly with the susceptibility of the strain to atherosclerosis.
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PMID:Age-related qualitative and quantitative changes in the endocrine pancreas of the LA/N-corpulent rat. 332 19


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