Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.11.13 (protein kinase C)
49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Integrating flame photometry was used for measuring sodium in single pancreatic islets from ob/ob mice. Exposure to 100 microM carbachol resulted in a 25-40% increase in sodium without any effect on potassium during incubation with 0-5 mM glucose in media deficient or not in Ca2+. This action of carbachol was abolished by 10 microM atropine or by raising the glucose concentration to 20 mM. A minor increase of the steady state content of sodium occurred in the presence of 200 microM ATP or 10 nM tetradecanoylphorbol 13-acetate (TPA). Carbachol differed from TPA in markedly stimulating sodium accumulation after ouabain inhibition of the Na/K pump. The results indicate that muscarinic receptor activation has opposite effects to glucose in inducing a rise of the islet content of sodium. It is suggested that the cholinergic control of the endocrine pancreas involves entry of Na+ in addition to the Na+ entry mediated by protein kinase C activation of Na+/H+ countertransport.
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PMID:Carbachol has opposite effects to glucose in raising the sodium content of pancreatic islets. 180 89

Rat adipocytes were treated with antisense dimethoxytrityl pentadecadeoxynucleotides, complementary to mRNA initiation codon regions for alpha and beta isozymes of protein kinase C (PKC). This antisense treatment provoked 50-70% decreases in PKC and insulin-stimulated 2-deoxyglucose uptake, but did not inhibit insulin-stimulated diacylglycerol synthesis. Sense or nonsense oligodeoxynucleotides were without effect on PKC and 2-deoxyglucose uptake. These results suggest that: (i) PKC-alpha and PKC-beta isozymes can be specifically downregulated in rat adipocytes by antisense oligodeoxynucleotides, and (ii) insulin-stimulated glucose transport requires PKC.
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PMID:Antisense DNA downregulates protein kinase C isozymes (beta and alpha) and insulin-stimulated 2-deoxyglucose uptake in rat adipocytes. 182 47

There seems to be little doubt that insulin rapidly perturbs phospholipid metabolism, and this appears to increase DAG/PKC signaling in many target tissues. Considerable new evidence further suggests that DAG/PKC signaling plays an important role in insulin-stimulated glucose transport. Further studies are needed to test this hypothesis and examine its importance in states of clinical insulin resistance.
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PMID:The role of diacylglycerol/protein kinase C signaling in insulin-stimulated glucose transport. 184 44

In Swiss 3T3 fibroblasts a peptide mitogen bombesin, which acts through the phospholipase C-protein kinase C signaling pathway, stimulates DNA synthesis in a manner strictly dependent on the medium calcium concentration: [3H]thymidine incorporation into DNA in the presence of a saturating concentration of bombesin (10(-8) M) is 4-fold greater at 3.0 mM extracellular calcium as compared with a value obtained at 0.03 mM calcium. In the present study we attempted to identify the site and the mechanism of action of Ca2+ influx along the bombesin-induced mitogenic signaling pathway, by comparing bombesin effects at 0.03 and 3.0 mM of medium calcium. Bombesin induces the same extent of increases in [3H]inositol phosphates after 1 min, and comparable sustained increases in the cellular content of 1,2-diacylglycerol for up to 4 h, at either 0.03 or 3.0 mM calcium. Bombesin induces the same extent of phosphorylation of MARCKS protein, the major cellular substrate for protein kinase C, irrespective of the medium calcium concentration for at least 4 h. Moreover, diverse cellular responses elicited by bombesin, including c-fos expression, activation of microtubule-associated protein 2 kinase and S6 kinase, glucose uptake, and protein synthesis but not the release of arachidonic acid and its metabolites, are induced similarly at either 0.03 or 3.0 mM calcium. Down-regulation of cellular protein kinase C nearly completely abolishes bombesin effects on c-fos expression, S6 kinase activation, glucose uptake, and DNA synthesis. These results suggest that the target of Ca2+ influx in bombesin-induced mitogenic signaling pathway is not located along the phospholipase C-protein kinase C signal transduction system including cellular events in early G1 phase that exist downstream to protein kinase C action.
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PMID:Role of Ca2+ influx in bombesin-induced mitogenesis in Swiss 3T3 fibroblasts. 184 53

Partially permeabilized rat adipocytes with a high responsiveness to insulin were prepared by electroporation and used to study the effect of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) on insulin actions in adipocytes. H-7 is a well-documented inhibitor of several protein kinases, including protein kinase C; however, it does not rapidly enter adipocytes protected with the intact plasma membrane. The cells were suspended in Buffer X [4.74 mM NaCl, 118.0 mM KCl, 0.38 mM CaCl2, 1.00 mM EGTA, 1.19 mM Mg2SO4, 1.19 mM KH2PO4, 25.0 mM Hepes/K, 20 mg/ml bovine serum albumin, and 3 mM pyruvate/Na, pH 7.4] and electroporated six times with a Gene-Pulser (from Bio-Rad) set at 25 microF and 2 kV/cm. In cells electroporated as above, insulin stimulated (a) membrane-bound, cAMP phosphodiesterase approximately 2.6-fold when the hormone concentration was 10 nM and (b) glucose transport activity approximately 4.5-fold when the hormone concentration was raised to 100 nM. H-7 strongly inhibited the actions of insulin on both glucose transport (apparent Ki = 0.3 mM) and cAMP phosphodiesterase (apparent Ki = 1.2 mM) in electroporated adipocytes. H-7 also inhibited lipolysis in adipocytes; the apparent Ki value for the reaction in intact cells was 0.45 mM, and that in electroporated cells was 0.075 mM. It is suggested that a certain protein kinase or kinases that are significantly sensitive to H-7 may be involved in the insulin-dependent stimulation of glucose transport and that of phosphodiesterase. However, protein kinase C (or Ca2+/phospholipid-dependent protein kinase) may not be involved, at least, in the hormonal action on phosphodiesterase since the apparent Ki value of H-7 for the reaction is too high.
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PMID:Evidence that protein kinase C may not be involved in the insulin action on cAMP phosphodiesterase: studies with electroporated rat adipocytes that were highly responsive to insulin. 184 37

Activation of protein kinase C (PKC) by bacterial lipopolysaccharide had recently been implicated in the pathogenetic sequence of gram-negative sepsis, endotoxicosis, hyperinsulinism, and the alterations in glucoregulation that eventuate in glucose dyshomeostasis. This study used the peptide antibiotic polymyxin B (PMX-B) and H-7, an isoquinoline sulfonamide, as inhibitors of PKC activation to evaluate responses to provocative insulin and glucose tolerance tests in control vs. endotoxic rats. Fed male rats were treated with either Salmonella enteritidis endotoxin (ETX; 0.33 mg/kg iv) or saline 120 min before intravenous insulin tolerance testing (IVITT) with human insulin (1 U/kg) or intravenous glucose tolerance testing (IVGTT) with D-glucose (1.2 g/kg). H-7 in dimethyl sulfoxide at 25 mg/kg, PMX-B in saline at 0.25 mg/kg, or the respective vehicles were administered 5 min before the tolerance tests. Neither H-7 nor PMX-B had any significant acute effects on basal plasma glucose or lactate values. The decline in plasma with IVITT was augmented by ETX; however, concomitant H-7 or PMX-B attenuated the insulin hypoglycemia. The computed half-life of glucose in the IVGTT was decreased by ETX; however, concomitant H-7 or PMX-B decreased the tolerance alteration. In addition, both H-7 and PMX-B attenuated the rise in insulin induced by the IVGTT. Thus the hyperinsulinism and the glucoregulatory disturbances in endotoxicosis may be mediated by PKC activation and ameliorated by PKC inhibition.
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PMID:Antagonism of endotoxic glucose dyshomeostasis by protein kinase C inhibitors. 185 53

Adipocytes are physiological targets for GH in both growing and nongrowing individuals. In adipocytes that have been deprived of GH for at least 3 h, GH initially produces a response that is characterized by increased metabolism of glucose and inhibition of the lipolytic effects of catecholamines. This insulin-like effect disappears within 2-3 h despite continued stimulation and cannot be elicited again unless cells are deprived of GH for at least 3 h. Despite refractoriness to the insulin-like action of GH, the lipolytic effect of GH is evident at this time. Although termination of the insulin-like response and induction of both refractoriness and lipolysis all depend upon synthesis of RNA and proteins, these 3 effects of GH appear to be neither temporally nor causally related. Scatchard analysis of ligand binding data suggests that these various effects are produced by interaction of GH with a single class of receptors. However, since modification of either the hormone or the carbohydrate moiety of the receptor can selectively attenuate either the insulin-like or the lipolytic response, more than one hormone receptor interaction is likely. Northern analysis indicates the presence of at least 2 alternately spliced mRNA transcripts for the GH receptor, and at least 3 different complexes are seen after GH is covalently crosslinked to intact adipocytes. Refractoriness does not result from changes in either the number or affinity of GH receptors, but may result from increased cytosolic calcium. Although the protein kinase C activator phorbol myristate acetate mimics both the insulin-like and lipolytic actions of GH, increased activity of protein kinase C probably does not mediate either action of GH. The intracellular mediators of the diverse actions of GH are unknown at this time.
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PMID:Cellular effects of growth hormone on adipocytes. 187 33

Quantitative autoradiography was used to examine the effect of lesioning a well-defined glutamatergic system (retinofugal fibres) on [3H]forskolin binding to Gs-adenylate cyclase and [3H]PDBu (phorbol-12,13-dibutyrate) binding to protein kinase C (PKC) in the rat visual system at 1, 5, 10 and 20 days after unilateral orbital enucleation. Local cerebral glucose utilisation was determined in the same animals using quantitative [14C]2-deoxyglucose autoradiography. At 5 days post-lesion, [3H]forskolin binding sites were significantly reduced in the visually-deprived superior colliculus (-14 +/- 1%) and dorsal lateral geniculate body (-8 +/- 2%), and these reductions persisted until 20 days post-lesion. There were no significant alterations in the amount of [3H]PDBu binding in any region in the visually-deprived hemisphere following enucleation. Function-related glucose use was significantly reduced throughout the visual pathway after enucleation. In this study, there was no conclusive evidence of plastic modifications of second messenger systems in the rat visual system despite a general depression of visual function following lesion of retinofugal fibres.
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PMID:Alterations of functional glucose use and ligand binding to second messenger systems following unilateral orbital enucleation. 188 25

Alterations of glucose metabolism and the oxidation of glutamine and palmitate were studied, by using specifically labelled substrates, in freshly isolated Kupffer cells and hepatic endothelial cells after infusion in vivo of human recombinant tumour necrosis factor-alpha (TNF; 7.5 x 10(5) IU/30 min per kg body wt., intravenously). Cells were incubated in a medium containing 5 mM-glucose, 0.4 mM-palmitate, 1 mM-lactate and 0.5 mM-glutamine. Administration of TNF in vivo increased glucose use in Kupffer cells by 70%. Glucose oxidation in the tricarboxylic acid cycle and flux in the Embden-Meyerhof (EM) pathway were elevated by 40 and 80% respectively. Treatment in vitro with 1 microM-phorbol 12-myristate 13-acetate (PMA) resulted in a similar percentage increase in glucose use by Kupffer cells prepared from either saline- or TNF-treated rats. However, PMA increased the activity of the hexose monophosphate shunt (HMS) by 3- and 10-fold in cells isolated from saline- or TNF-infused animals respectively. A phagocyte stimulus in vitro, opsonized zymosan, increased glucose use by 30% and doubled the flux through the HMS in Kupffer cells from saline-infused animals. The activity of the HMS in response to zymosan was increased by 400% after TNF treatment. In endothelial cells, basal glucose utilization was not altered by TNF treatment. PMA increased HMS activity in endothelial cells to a similar degree after saline or TNF infusion. Zymosan, however, increased HMS activity only in endothelial cells from TNF-treated rats. Oxidation of palmitate or glutamine was not affected by TNF treatment either under basal conditions or after challenge in vitro. Our data indicate that, after phagocytosis in vitro or protein kinase C activation, glucose use and flux through the HMS increase in Kupffer cells. This is accompanied by increased glycolytic flux, with no changes in glucose oxidation in the tricarboxylic acid cycle. After TNF exposure, followed by a secondary stimulus, the enhanced glucose use by Kupffer cells is primarily channelled through the HMS pathway. These data suggest that the increased glucose use in vivo by Kupffer cells found after immune-stimulated conditions may subserve primarily the increased need for NADPH and HMS intermediates.
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PMID:Up-regulation of glucose metabolism in Kupffer cells following infusion of tumour necrosis factor. 189 44

Glyburide and tolbutamide, at concentrations of 20 to 40 mumol/L and 1 to 2 mmol/L, respectively, stimulated glucose transport in rat adipocytes. Concomitantly, protein kinase C was activated, as evidenced by translocation of immunoreactive enzyme from cytosol to membranes. Glucose transport effects of the sulfonylureas were blocked by three inhibitors of protein kinase C (H-7, staurosporine, and sangivamycin), and by phorbol ester-induced down-regulation of protein kinase C. These findings suggest that sulfonylureas may stimulate glucose transport in rat adipocytes through activation of protein kinase C.
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PMID:Sulfonylureas activate glucose transport and protein kinase C in rat adipocytes. 189 24


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