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)

The effects of hormones and cytokines on angiotensinogen production were studied in primary cultured rat hepatocytes. The basal secretion of angiotensinogen decreased during culture. The addition of dexamethasone and (Bu)2cAMP completely prevented this decrease. Angiotensinogen secretion by freshly plated hepatocytes was slightly increased in response to dexamethasone, but after 24 h in culture, hepatocytes no longer responded to dexamethasone alone. When hepatocytes were treated with (Bu)2cAMP, glucagon, or forskolin, angiotensinogen secretion increased in response to dexamethasone in a concentration-dependent manner. 17 beta-Estradiol and T3 failed to stimulate angiotensinogen secretion in either the presence or absence of (Bu)2cAMP. Interleukin-6 (IL-6) exhibited a stimulatory activity on angiotensinogen secretion, which was dependent on the presence of dexamethasone, whereas IL-1 and tumor necrosis factor had no effect in either the presence or absence of dexamethasone and/or (Bu)2cAMP. Unlike primary cultured hepatocytes, angiotensinogen secretion by rat hepatoma H4IIEC3 cells increased in response to dexamethasone alone. This increase was not enhanced by (Bu)2cAMP, but was enhanced by IL-6. Thus, in primary cultures of rat hepatocytes, neither glucocorticoid, cAMP, nor IL-6 alone stimulated angiotensinogen production, but a combination of glucocorticoid and cAMP or of glucocorticoid and IL-6 exhibited a stimulatory activity on angiotensinogen production. These results suggest that angiotensinogen production in the liver is synergistically regulated by these factors, whereas the hepatoma cell line H4IIEC3 lacks the regulatory mechanism of cAMP on glucocorticoid-induced angiotensinogen production.
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PMID:Stimulation of angiotensinogen production in primary cultures of rat hepatocytes by glucocorticoid, cyclic adenosine 3',5'-monophosphate, and interleukin-6. 131 Dec 38

Glucocorticoid regulation of peptide hormone gene expression was studied in two cell lines derived from rodent islet cell tumors. In rat RIN1056A cells, dexamethasone reduced the levels of glucagon mRNA transcripts while markedly inducing the expression of the angiotensinogen gene. In contrast, dexamethasone had no effect on the regulation of glucagon gene expression in hamster InR1-G9 cells. Wild type InR1-G9 cells did not support the induction of the murine mammary tumor virus promoter by glucocorticoids, suggesting that these cells lacked the necessary cellular factor(s) for glucocorticoid responsiveness. Introduction of the glucocorticoid receptor into wild type InR1-G9 cells restored glucocorticoid induction of the murine mammary tumor virus promoter, but not glucocorticoid regulation of glucagon gene expression. Dexamethasone treatment of Sprague-Dawley rats had no effect on the levels of pancreatic glucagon mRNA transcripts. The results of these studies demonstrate that glucocorticoid regulation of glucagon gene expression is restricted to the immortalized RIN1056A cell line, providing additional evidence for cell-specific diversity in the regulation of peptide hormone gene expression in neuroendocrine tumors.
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PMID:Differential glucocorticoid regulation of glucagon gene expression in cell lines derived from rat and hamster islet cell tumors. 170 69

The role of intracellular messengers in the stimulatory effect of angiotensin II on angiotensinogen synthesis and secretion in hepatocytes was examined. Angiotensinogen secretion was not influenced by modulators of intracellular calcium (calmidazolium, A 23187, Bay K 8644, methoxamine). In contrast, agents decreasing intracellular cAMP (angiotensin II, guanfacine) stimulated, and those increasing cAMP (isoproterenol, glucagon, forskolin) depressed angiotensinogen secretion. An inverse relationship was also observed between cAMP and angiotensinogen mRNA. Pretreatment of hepatocytes with pertussis toxin abolished the stimulation by angiotensin II. It is concluded that angiotensin II-induced stimulation of angiotensinogen synthesis is initiated by inhibition of adenylate cyclase.
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PMID:Angiotensin II stimulates angiotensinogen synthesis in hepatocytes by a pertussis toxin-sensitive mechanism. 215 83

The cellular mechanism by which the angiotensin II (AII) agonist, Sar1-AII, inhibits production and release of angiotensinogen in human hepatoma HepG2 cells was examined. Pretreatment of HepG2 cells with pertussis toxin attenuated the ability of Sar1-AII to block angiotensinogen production. This effect could be correlated with the in situ ADP-ribosylation of a protein(s) of apparent molecular weight 39,000-41,000 on SDS-PAGE, and attenuation of the ability of Sar1-AII to inhibit cAMP accumulation. The role of cAMP in angiotensinogen production was examined. A transient increase in cAMP accumulation above basal could be evoked by forskolin (8-fold) or by glucagon (5-fold) using insulin-deficient media. Although neither forskolin nor glucagon had a significant effect on angiotensinogen production agents producing a sustained increase in intracellular cAMP (8-bromo-cAMP, dibutyryl-cAMP, cholera toxin) were able to increase angiotensinogen production. Although these data indicate that intracellular cAMP is a regulatory factor in angiotensinogen production other evidence suggests that modulation of intracellular cAMP is not entirely responsible for the effects of Sar1-AII.
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PMID:Involvement of a pertussis toxin-sensitive G protein in the regulation of angiotensinogen production by an angiotensin II analog in HepG2 cells. 217 1

Proglucagon is a polyprotein precursor containing not only glucagon and glicentin, but glucagon-like peptides-I and -II and an intervening peptide (IP-II). The glucagon gene is expressed in both pancreatic islets and neuroendocrine L-cells of the gastrointestinal tract. We have recently cloned an islet cell line from a rat pancreatic islet cell tumour that simultaneously expresses the glucagon, insulin, somatostatin, and angiotensinogen genes. We investigated the potential role of "second messenger" pathways in the regulation of glucagon gene expression. Both the tumor promoter agent phorbol myristate acetate (PMA) and a diacylglycerol analog, 1,2-dioctanoylglycerol, induced a 2.7- and 2.5-fold increase in steady-state glucagon mRNA levels at 24 h, respectively. The increase was progressive up to 24 h and was specific for glucagon mRNA; the insulin and somatostatin mRNA levels remained unchanged. An inactive phorbol ester, 4 beta-phorbol 12,13,20-triacetate, was without effect. The glucagon mRNA increase induced by PMA was mediated through an increase in glucagon gene transcription reaching maximal stimulation at 30-60 min. Glucagon mRNA half-life was similar in both control and PMA-treated cells, approximating 12 h. The stimulation of glucagon gene transcription was accompanied by a corresponding 3-fold increase in proglucagon biosynthesis. Neither dibutyryl cAMP nor glucocorticoids affected glucagon mRNA levels, while inducing a 5-fold increase in somatostatin mRNA levels and 4.8-fold stimulation in angiotensinogen mRNA at 24 h, respectively. We conclude that expression of the glucagon gene in this islet cell line is regulated at the level of transcription through a protein kinase C (Ca2+/phospholipid-dependent enzyme)-activated pathway.
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PMID:Glucagon gene transcription in an islet cell line is regulated via a protein kinase C-activated pathway. 287 43

The developmental origin of the four phenotypically distinct hormone-producing islet cells (insulin, glucagon, somatostatin, pancreatic polypeptide) is unclear. To investigate the potential for phenotypic differentiation of islet cells, we prepared several clonal cell lines from a radiation-induced rat islet tumor and analyzed them for insulin, glucagon, and somatostatin gene expression by cDNA hybridization, immunocytochemistry, and radioimmunoassay. We found expression of all three genes in the tumor and in the parental cell line and mixed variable phenotypes in the clonal lines derived from the parental line. We also observed the ectopic expression of the angiotensinogen gene in the tumor and the cell lines. The relative levels of hormonal gene expression differed among the cell lines but remained fixed during continuous passage. The three islet hormone mRNAs were larger compared to the pancreas owing to longer poly(A) tracts. These observations indicate that neoplastic islet cells retain the potential to differentiate into hormone-specific cellular phenotypes and may mimic developmental pathways of the pancreatic islets.
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PMID:Multipotential phenotypic expression of genes encoding peptide hormones in rat insulinoma cell lines. 287 52

The state of differentiation of various neoplastic cell lines is inversely correlated with the rate of cellular growth. To delineate the changes in hormone gene expression associated with an induced decrease in the growth rate of rat insulinoma cells, we studied the effects of sodium butyrate on the expression of the genes encoding insulin, glucagon, and angiotensinogen. Sodium butyrate inhibited cellular proliferation and decreased levels of c-myc mRNA. Concomitantly, steady-state levels of mRNAs encoding insulin and glucagon increased by 10- and 8.5-fold, respectively, as a result of a specific increase in the transcription of both genes. Sodium butyrate also inhibited angiotensinogen gene expression, which was ectopic in the insulinoma cells. These observations suggest that sodium butyrate induces a pattern of events leading to the differentiation of the rat insulinoma cells.
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PMID:Transcriptional regulation of genes encoding insulin, glucagon, and angiotensinogen by sodium butyrate in a rat islet cell line. 355 Apr 24

We have purified an ATP-dependent protease with protein-dependent ATPase activity from bovine adrenal cortex mitochondria to near homogeneity. The subunit molecular weight is 108,000 and the enzyme appears to be a hexamer with approximately identical subunits. Based on the experiments using various nucleoside triphosphates and their related compounds, it is concluded that hydrolysis of the high-energy bond in nucleoside triphosphates is not an absolute requirement for proteolysis. Nucleotide specificity of this enzyme varies, depending on the protein or peptide substrates used. When casein was the substrate, ATP and dATP were quite effective, but other nucleotides were not. When insulin and angiotensinogen were used as substrate, ATP, other nucleoside triphosphates, ADP, inorganic triphosphate, pyrophosphate, and phosphate were effective. One of the cleaving linkages hydrolyzed by this enzyme was revealed to be the Leu-Leu bond of angiotensinogen. However, the specificity appears to be broad in view of the hydrolysis pattern of glucagon.
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PMID:Adrenal cortex mitochondrial enzyme with ATP-dependent protease and protein-dependent ATPase activities. Purification and properties. 390 33

Renin-like activity (RLA) and angiotensin I-converting enzyme-like activity (ACELA), two key enzymes of the renin-angiotensin cascade (RAS), were sought in the dogfish rectal gland. RLA was 1.1 +/- 0.2 ng Ang I/mg protein/hr after incubation with porcine angiotensinogen and 0.8 +/- 0.1 ng Ang I/mg protein/hr after incubation with homologous plasma. ACELA was 7.22 +/- 1.08 and 8.87 +/- 1.9 nmol hippurate generated/min/mg protein respectively, at 0 and 37 degrees. The presence of these enzymes may indicate the presence of an endogenous RAS-like system in the rectal gland. Angiotensin II (Ang II) and atrial natriuretic peptide (ANP) binding sites were demonstrated autoradiographically in the subcapsular region of the gland, suggesting a possible interaction of the two hormones in the blind outer ends of the rectal gland tubules. Immunoreactivities toward Ang II, ANP, bombesin, vasoactive intestinal polypeptide (VIP), glucagon, and somatostatin were differentially localized in the rectal gland within three concentric zones with potentially different functional activities. In the capsule, there was a strong positive ir-glucagon reaction and a slightly weaker reaction for ir-somatostatin and VIP. In the blind outer ends of the tubules (in the subcapsular zone), strong immunoreactivity was present toward all the tested peptides except glucagon and somatostatin. In the inner zone and in the central canal, only a weak immunoreactivity toward Ang II and glucagon was observed.
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PMID:Renin-like activity, angiotensin I-converting enzyme-like activity, and osmoregulatory peptides in the dogfish rectal gland. 790 83

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been used for C-terminal amino acid sequence determination of peptides and proteins. The usefulness of MALDI-MS was demonstrated by analyzing peptide mixtures (C-terminal peptide ladder) which were generated by enzymatic digestion of substance P, glucagon, angiotensinogen, insulin B chain and myoglobin with the exopeptidases carboxypeptidase Y and P. The results clearly show that up to 11 amino acid residues can be determined in the pmol range by analyzing the molecular masses of the truncated peptides. For proteins it is possible to investigate enzymatic or chemical digests in the same manner.
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PMID:MALDI-MS for C-terminal sequence determination of peptides and proteins degraded by carboxypeptidase Y and P. 800 81


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