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

The non-tumoral endocrine pancreas from a patient with elevated plasma levels of glucagon due to a malignant glucagonoma was studied immunocytochemically, ultrastructurally and morphometrically. Compared with normal pancreatic islets from control subjects, those of the pancreas from the patient with a glucagonoma showed an almost complete disappearance of A cells, a decrease in immunoreactive insulin in B cells associated with cytological features indicating enhanced synthesis and secretion of this hormone, and an increase in immunoreactive somatostatin and pancreatic polypeptide (PP) accompanied by unusually high numbers of D and PP cells. In addition, numerous B cells were found outside the islets, either forming micro-islets or scattered in the exocrine tissue (nesidioblastosis). The possible mechanisms involved in determining the changes in the secretory activity of B cells and the alterations in the cell composition of the islets are discussed.
Virchows Arch B Cell Pathol Incl Mol Pathol 1991
PMID:Morphological changes in the human endocrine pancreas induced by chronic excess of endogenous glucagon. 167 71

Glucagon increased alanine amino transferase (AAT) activity in perfused rat liver by about 90% over control. Propranolol, the beta receptor antagonist, abolished the effect of glucagon on this enzyme. Well known beta receptor agonists like isoproterenol, norepinephrine and epinephrine also increased the enzyme activity under identical condition and the enhancement was similarly abolished by propranolol. These experiments suggest that the effect of glucagon on AAT was mediated through beta adrenergic receptor. However, the interesting observation was that phenylephrine, alpha receptor agonist and phenoxybenzamine and tolazoline, two alpha receptor antagonists, increased the AAT activity like glucagon in perfusion experiments and the effects of all these three agents were also abolished by propranolol. Glucagon, when perfused with phenoxybenzamine showed some additive effect. From all these results we are proposing that in our system phenoxybenzamine is acting as beta agonist although it is known to be an alpha antagonist.
Mol Cell Biochem 1991 Jun 26
PMID:Effect of glucagon and some other alpha and beta adrenergic agonists and antagonists on alanine amino transferase of perfused rat liver. 168 19

This study examines the behavior of glycogen-storing rat hepatoma (N13) in vitro using cytophotometric techniques. A significant increase in glycogen is observed in these cells after 30 min incubation in a buffered solution containing 0.1 mM glucose, that is 80 times lower than the physiological glucose concentration in rat blood. N13 hepatoma cells grow exponentially in culture using RPMI 1640 tissue culture medium supplemented with 10% fetal bovine serum. During the first day in culture these cells store a large amount of glycogen and this increase is also observed in serum-free cultures. In more prolonged cultures the amount of glycogen per cell gradually becomes lower, although the culturing conditions are maintained. Similar variations of protein are also observed during the initial period of culture. DNA distribution does not show significant changes, although in serum-free cultures an increase in the proportion of cells in S and G2/M phases is observed. The addition of glucagon, epinephrine and cyclic AMP derivatives to serum-free cultures does not impede the storage of glycogen. Nevertheless, addition of either 2 mM N6,O2'-dibutyryl cyclic AMP or 0.1 mM 8-(4-chlorophenylthio)-cyclic AMP blocks the cell cycle at G0/G1 and glycogen content does not decrease after the first day in culture. We believe that this cell line offers an appropriated model to study glycogen metabolism and its involvement in the neoplastic process.
Virchows Arch B Cell Pathol Incl Mol Pathol 1991
PMID:Cytophotometric analysis of glycogen, protein and DNA of a glycogen-storing rat hepatoma (N13) cell line. 168 17

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.
Mol Endocrinol 1991 Oct
PMID:The pancreatic islet-specific glucagon G3 transcription factors recognize control elements in the rat somatostatin and insulin-I genes. 168 54

We have previously demonstrated that glucagon but not dexamethasone could induce serine dehydratase (SDH: EC.4.2.1.13) in liver, and either glucagon or dexamethasone could induce the enzyme in kidney of normal rats. The mechanism(s) of the hormonal regulation of SDH gene expression in liver and kidney was further studied using adrenalectomized rats. Simultaneous administration of glucagon and dexamethasone induced the activity, rate of SDH synthesis, and accumulation of SDH mRNA in both liver and kidney of the rat. The increased SDH activity was reflected by changes in the amount of enzyme protein and in the rate of SDH protein synthesis, both parameters closely paralleling the changes in the levels of SDH mRNA. The rates of transcription of the SDH gene as measured in run-on experiments with isolated nuclei were also increased by the administration of these hormones. These results indicate that the expression of the SDH gene was regulated primarily at the transcriptional level under these conditions. When glucagon or dexamethasone was injected separately into adrenalectomized rats, significant increases in the levels of SDH mRNA and the rate of SDH gene transcription were observed in liver. Although glucagon was more effective than dexamethasone, both hormones were required for the maximal induction of SDH gene transcription in liver. In contrast, dexamethasone alone effectively increased the rate of SDH gene transcription in kidney.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1991 Nov
PMID:Hormonal regulation of serine dehydratase gene expression in liver and kidney of the adrenalectomized rat. 177 69

Highly sulfated, heparinlike species of heparan sulfate proteoglycans, with heparinlike glycosaminoglycan chains, are extracellular matrix components that are plasma membrane bound in growth-arrested liver cells. Heparins were found to inhibit the growth and lower the clonal growth efficiency of HepG2, a minimally deviant, human hepatoma cell line. Heparan sulfates, closely related glycosaminoglycans present in the extracellular matrix around growing liver cells, had no effect on the growth rate or clonal growth efficiency of HepG2 cells. Neither heparins nor heparan sulfates had any effect on the growth rate or clonal growth efficiency of two poorly differentiated, highly metastatic hepatoma cell lines, SK-Hep-1 and PLC/PRF/5. Heparin's inhibition of growth of HepG2 cells correlated with changes in the mRNA synthesis and abundance of insulinlike growth factor II (IGF II) and transforming growth factor beta (TGF beta). HepG2 cells expressed high basal levels of mRNAs encoding IGF II and TGF beta that were inducible, through transcriptional and posttranscriptional mechanisms, to higher levels by specific heparin-hormone combinations. For both IGF II and TGF beta, the regulation was multifactorial. Transcriptionally, IGF II was regulated by the additive effects of insulin, glucagon, and growth hormone in combination with heparin; TGF beta was regulated primarily by the synergistic effects of insulin and growth hormone in combination with heparin. Posttranscriptionally, the mRNA abundance of the IGF II 4.5- and 3.7-kb transcripts was affected by insulin. Heparin induction of all IGF II transcripts was also dependent on triiodotyronine and prolactin, but it is unknown whether their induction by heparin was via transcriptional or posttranscriptional mechanisms. Heparin-insulin combinations regulated TGF beta posttranscriptionally. The poorly differentiated hepatoma cell lines PLC/PRF/5 and SK-Hep-1 either did not express or constitutively expressed low basal levels of IGF I, IGF II, and TGF beta, whose mRNA synthesis and abundance showed no response to any heparin-hormone combination. We discuss the data as evidence that matrix chemistry is a variable determining the expression of autocrine growth factor genes and the biological responses to them.
Mol Cell Biol 1991 Jan
PMID:Heparin and hormonal regulation of mRNA synthesis and abundance of autocrine growth factors: relevance to clonal growth of tumors. 184 19

The pancreatic beta-cell is a major site of islet amyloid polypeptide (IAPP) biosynthesis, and the peptide is coreleased with insulin. We have analyzed the expression of IAPP (mRNA and protein) in various cell types in normal and transformed murine islet cell cultures by Northern blot analyses and immunocytochemistry. IAPP is primarily coexpressed with insulin in the beta-cell of GH-promoted primary rat islet cell cultures. Additionally, a small population of non-beta-cells exhibited a prominent IAPP expression, and double staining experiments showed colocalization with glucagon or somatostatin in some of these cells. IAPP mRNA was confined to the beta-cell phenotype when analyzing the phenotypically stable in vivo tumor lines, MSL-G2-IN (insulinoma) and MSL-G-AN (glucagonoma), and the transgenic mouse islet cell lines, beta-Tc and alpha-Tc. However, IAPP and insulin expression were completely uncoupled in unstable heterogeneous clones such as NHI-6F. This clone is composed of primarily glucagon-producing cells in vitro, but insulin gene expression becomes dominant after passage in vivo. Interestingly, IAPP was hyperexpressed with glucagon under in vitro conditions in this clone. We conclude that the tissue specificity of expressions of IAPP and insulin are controlled differently, and that coexpression of IAPP with hormones different from insulin may be a marker for pluripotent transformed rat islet cell clones, which are able to activate insulin gene transcription during passage in vivo.
Mol Endocrinol 1991 Jan
PMID:Islet amyloid polypeptide and insulin expression are controlled differently in primary and transformed islet cells. 185 Jan 7

In the mouse insulin is first detected on embryonic day 12 (e12) in a subpopulation of the cells that on e10 start to produce glucagon. During the continued embryonic development, the number of cells that coexpress the two hormones is gradually decreased, and in adults the expression of these two hormone genes is segregated to the beta- and alpha-cells. To begin to understand the process of terminal differentiation that restricts insulin gene expression to beta-cells, we have assayed for the presence of nuclear proteins that interact with transcriptional regulatory sequences of the rat insulin I gene in pancreatic alpha- and beta-cell lines. All except one of the previously identified insulin enhancer-binding proteins were found to be present in both cell types. A new insulin promoter-binding protein, IPF1, which was present in beta-cells but absent in alpha-cells, was identified. The beta-cell specificity of IPF1 implies that the insulin promoter is involved in the restriction of insulin gene expression to the beta-cells. The binding sites for IPF1 and the beta-cell-specific enhancer-binding protein IEF2 are both recognized by the previously isolated homeodomain-containing LIM protein isl-1, but these three proteins were all shown to be different entities.
Mol Endocrinol 1991 Jul
PMID:Novel insulin promoter- and enhancer-binding proteins that discriminate between pancreatic alpha- and beta-cells. 194 96

The 5'-flanking region of the rat glucagon gene contains, from nucleotides -291 to -298, a sequence (TGA CGTCA) which mediates cyclic AMP (cAMP) responsiveness in several genes (cAMP-responsive element [CRE]). However, because of nonpermissive bases surrounding the CRE octamer, the glucagon CRE does not confer cAMP responsiveness to an inert heterologous promoter in placental JEG cells that do not express the glucagon gene. This report describes transient transfection experiments with glucagon-reporter fusion genes that show that glucagon gene expression is activated by cAMP-dependent protein kinase A in a glucagon-expressing pancreatic islet cell line. This activation is mediated through the glucagon CRE.
Mol Cell Biol 1990 Dec
PMID:Transcriptional activation of the rat glucagon gene by the cyclic AMP-responsive element in pancreatic islet cells. 214 27

We used Ha-ras-transformed Madin-Darby canine kidney (MDCK) cells as a model to study possible signal transduction mechanisms underlying the induction of glucagon responsiveness by the differentiation inducers prostaglandin E2 (PGE2) and 8-bromo-cyclic (8-Br-cAMP) AMP and the inhibition of induction by phorbol ester or a serum factor. The steady-state level of inositol 1,4,5-trisphosphate (IP3) was higher in Ha-ras-transformed MDCK cells than in parental MDCK cells. In contrast, the steady-state level of intracellular cAMP of transformed cells was similar to that of normal cells. PGE2 and 8-Br-cAMP increased cAMP content but decreased IP3 levels in a concentration-dependent fashion after 5 days of treatment. We examined the time course for effects of PGE2 and 8-Br-cAMP and found that there was a lag period of 8 to 16 h between elevation of cAMP after the addition of 8-Br-cAMP or PGE2 and the decrease of IP3 levels. Another lag period of 2 days existed before the induction of differentiation. Both the reduction of IP3 levels and the induction of glucagon responsiveness were blocked by phorbol-12-myristate-13-acetate or serum, suggesting that a decrease in the IP3 level might be causally involved in induction of differentiation in transformed MDCK cells. However, induction of differentiation was not due to changes in the expression or guanine nucleotide-binding properties of p21 protein. It is likely that cAMP has a direct regulatory effect on the phospholipid signaling pathway. We conclude that perturbation of the inositol phosphate signaling pathway may be responsible for the induction of differentiation by PGE2 and 8-Br-cAMP in transformed MDCK cells.
Mol Cell Biol 1990 Jan
PMID:Induction of differentiation in v-Ha-ras-transformed MDCK cells by prostaglandin E2 and 8-bromo-cyclic AMP is associated with a decrease in steady-state level of inositol 1,4,5-trisphosphate. 215 66


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