Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The possible role of cAMP and/or arachidonic acid (and metabolites) in the stimulation of glucose transport elicited by bradykinin in Swiss 3T3 fibroblasts was investigated with particular attention to the part of this effect inhibitable by pertussis toxin. Application of the membrane permeant cAMP analog 8-BrcAMP modified neither basal nor stimulated transport observed after bradykinin, insulin, or the combination of the two, indicating that [cAMP]i fluctuations are probably not involved. In contrast, arachidonic acid, which is released by the cells exposed to bradykinin, was able to markedly stimulate glucose transport, however, only at relatively high concentrations (EC50 approximately 30 microM). The stimulation by arachidonic acid was insensitive to pertussis toxin and was largely inhibited by both the cyclooxygenase blocking drug, indomethacin, and the [Ca2+]i clamping at the resting level (by ionomycin administered in a Ca2(+)-free incubation medium). Neither of the last treatments affected the glucose transport activated by bradykinin to a great extent. Moreover, the bradykinin-induced arachidonic acid release was unaffected by pertussis toxin and markedly inhibited by two treatments ineffective on glucose transport, the blockade of [Ca2+]i increases elicited by the peptide and the administration of the phospholipase A2 blocker, quinacrine. These results exclude that glucose transport stimulation by bradykinin is mediated intracellularly via arachidonic acid release. Since the involvement of Ca2+ and diacylglycerol can also be ruled out by present and previous results, this effect of the peptide appears to be independent of the generation of known second messengers and might be triggered by the direct interaction of a pertussis toxin-sensitive G protein with the glucose transporter in the plane of the plasma membrane.
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PMID:Glucose transport stimulation by bradykinin in Swiss 3T3 fibroblasts: a pertussis toxin-sensitive mechanism operates without involvement of arachidonic acid and cyclic AMP. 184 1

Isolated muscle cells from adult rat heart were used to study the involvement of G-proteins in the regulation of the glucose transporter by insulin and isoprenaline. Efficient modification of G-protein functions was established by measuring isoprenaline-stimulated cyclic AMP production, viability and ATP content after treating the cells with cholera toxin and pertussis toxin for 2 h. Under these conditions cholera toxin decreased the stimulatory action of insulin on 3-O-methylglucose transport by 56%, but pertussis toxin had no effect. Basal transport was not affected by toxin treatment. Isoprenaline increased 3-O-methylglucose transport by 63%. This effect was not mimicked by dibutyryl cyclic AMP, but was completely blocked by cholera toxin. Streptozotocin-diabetes abolished isoprenaline action and decreased stimulation of transport by 64%. Concomitantly, cholera-toxin sensitivity of glucose transport was lost in cells from diabetic animals. This was paralleled by a large decrease (87 +/- 4%) in mRNA expression of the insulin-regulatable glucose transporter, as shown by Northern-blot analysis of RNA isolated from cardiomyocytes of diabetic rats. These data suggest a functional association between the insulin-responsive glucose transporter and a cholera-toxin-sensitive G-protein mediating stimulation by insulin and isoprenaline.
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PMID:G-protein-mediated regulation of the insulin-responsive glucose transporter in isolated cardiac myocytes. 217 73

Glucose transport stimulation by insulin, bombesin, and bradykinin in Swiss 3T3 fibroblasts was compared with the phosphoinositide hydrolysis effects of the same stimulants in a variety of experimental paradigms known to affect generation and/or functioning of intracellular second messengers: short- and long-term treatments with phorbol dibutyrate, that cause activation and down-regulation of protein kinase C, respectively; cell loading with high [quin2], that causes clamping of [Ca2+]i near the resting level; poisoning with pertussis toxin, that affects the GTP binding proteins of the Go/Gi class; treatment with Ca2+ ionophores. Glucose transport stimulation by maximal [insulin] was affected by neither pertussis toxin nor protein kinase C down-regulation. The latter, however, partially blocked the action of suboptimal [insulin]; moreover, acute phorbol dibutyrate treatment caused responses more than additive at all [insulin]. Thus, the insulin action on glucose transport in 3T3 cells appears to be synergistically potentiated by a protein kinase C-dependent mechanism, and not directly mediated by the enzyme. This result correlates with the lack of effect of insulin on phosphoinositide hydrolysis. In contrast, part of the glucose transport responses induced by bombesin and bradykinin appeared to be mediated by protein kinase C in proportion with the stimulation induced by these peptides on the phosphoinositide hydrolysis. The protein kinase C-independent portion of the response to bradykinin was found to be inhibitable by pertussis toxin. This latter result might suggest an interaction between the bradykinin receptor and a glucose transporter, mediated by a protein of the Go/Gi class.
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PMID:Regulation of glucose transport by insulin, bombesin, and bradykinin in Swiss 3T3 fibroblasts: involvement of protein kinase C-dependent and -independent mechanisms. 254 Oct 5

Endothelin-1 (ET-1) can stimulate insulin-responsive glucose transporter (GLUT4) translocation in 3T3-L1 adipocytes (Wu-Wong, J. R., Berg, C. E., Wang, J., Chiou, W. J., and Fissel, B. (1999) J. Biol. Chem. 274, 8103-8110), and in the current study, we have evaluated the signaling pathway leading to this response. First, we inhibited endogenous Galpha(q/11) function by single-cell microinjection using anti-Galpha(q/11) antibody or RGS2 protein (a GTPase activating protein for Galpha(q)) followed by immunostaining to quantitate GLUT4 translocation in 3T3-L1 adipocytes. ET-1-stimulated GLUT4 translocation was markedly decreased by 70 or 75% by microinjection of Galpha(q/11) antibody or RGS2 protein, respectively. Pretreatment of cells with the Galpha(i) inhibitor (pertussis toxin) or microinjection of a Gbetagamma inhibitor (glutathione S-transferase-beta-adrenergic receptor kinase (GST-BARK)) did not inhibit ET-1-induced GLUT4 translocation, indicating that Galpha(q/11 )mediates ET-1 signaling to GLUT4 translocation. Next, we found that ET-1-induced GLUT4 translocation was inhibited by the phosphatidylinositol (PI) 3-kinase inhibitors wortmannin or LY294002, but not by the phospholipase C inhibitor U-73122. ET-1 stimulated the PI 3-kinase activity of the p110alpha subunit (5.5-fold), and microinjection of anti-p110alpha or PKC-lambda antibodies inhibited ET-stimulated GLUT4 translocation. Finally, we found that Galpha(q/11) formed immunocomplexes with the type-A endothelin receptor and the 110alpha subunit of PI 3-kinase and that ET-1 stimulation enhances tyrosine phosphorylation of Galpha(q/11). These results indicate that: 1) ET-1 signaling to GLUT4 translocation is dependent upon Galpha(q/11) and PI 3-kinase; and 2) Galpha(q/11) can transmit signals from the ET(A) receptor to the p110alpha subunit of PI 3-kinase, as does insulin, subsequently leading to GLUT4 translocation.
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PMID:Endothelin-1-induced GLUT4 translocation is mediated via Galpha(q/11) protein and phosphatidylinositol 3-kinase in 3T3-L1 adipocytes. 1055 59

Heterotrimeric G-proteins, including Galpha(i2), have been implicated in modulating glucose disposal and insulin signaling. This cross-talk between G-protein-coupled and tyrosine kinase-coupled signaling pathways is a focal point for the study of integration of cell signaling. Herein we study the role of Galpha(i2) in modulating glucose transport, focusing upon linkages to insulin signaling. Utilizing mice harboring a transgene that directs the expression of a constitutively activated, GTPase-deficient mutant of Galpha(i2) (Q205L) in adipose tissue, skeletal muscle, and liver, we demonstrate that Galpha(i2) regulates the translocation of the insulin-sensitive GLUT4 glucose transporter in skeletal muscle and adipose tissue. The expression of Q205L Galpha(i2) increased glucose transport and translocation of GLUT4 to the plasma membrane in vivo in the absence of insulin stimulation. Adipocytes from the Q205L Galpha(i2) mice displayed enhanced insulin-stimulated glucose transport and GLUT4 translocation to the plasma membrane to levels nearly twice that of those from littermate controls. Phosphatidylinositol 3-kinase and Akt activities were constitutively activated in tissues expressing the Q205L Galpha(i2). Studies of adipocytes from wild-type mice displayed short term activation of phosphatidylinositol 3-kinase, Akt, and GLUT4 translocation in response to activation of Galpha(i2) by lysophosphatidic acid, a response sensitive to pertussis toxin. These data provide an explanation for the marked glucose tolerance of the Q205L Galpha(i2) mice and demonstrate a linkage between Galpha(i2) and GLUT4 translocation.
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PMID:Galpha i2 enhances in vivo activation of and insulin signaling to GLUT4. 1145 61

Mastoparan, a tetradecapeptide purified from wasp venom, has been shown to stimulate glucose transport in rat adipocytes although the mechanism of its action has remained undefined. Here, we characterized the action of mastoparan on glucose transport in rat adipocytes. Mastoparan at a concentration of 20 microM or more caused a dose-dependent release of lactate dehydrogenase (LDH) from the cells, which closely correlated with its stimulatory effect on glucose uptake. The mastoparan-induced glucose uptake was inhibited neither by deprivation of ATP with KCN nor by addition of phloretin, a direct inhibitor of glucose transporter, suggesting that the ability of mastoparan to stimulate glucose uptake did not derive from activation of the glucose transport system (i.e. translocation or activation of GLUT4 and/or GLUT1). On the other hand, mastoparan at a lower concentration (15 microM or below), which showed an insignificant effect on LDH release, potentiated the insulin action on glucose transport and Akt phosphorylation in the presence of adenosine deaminase. The effect of mastoparan was not additive to that of phenylisopropyladenosine and was completely abolished by pretreatment of adipocytes with pertussis toxin (1 microg/ml for 2 hours). Thus, the present study disclosed duality in the action of mastoparan on glucose uptake in rat adipocytes. At a concentration of 15 microM or less, it enhances the insulin action on glucose transport by a pertussis toxin-sensitive Gi protein-dependent mechanism. At higher concentrations, however, mastoparan increases non-specific permeability of the plasma membrane, which causes LDH release as well as glucose uptake not mediated through glucose transporter.
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PMID:Duality in the mastoparan action on glucose transport in rat adipocytes. 1612 6

Mounting evidence suggests that the endocannabinoid system regulates energy metabolism through direct effects on peripheral tissues as well as central effects that regulate appetite. Here we examined the effect of cannabinoid receptor 1 (CB1) signaling on insulin action in fat cells. We examined effects of the natural CB1 agonist, 2-Arachidonoylglycerol (2-AG), and the synthetic CB1 antagonist, SR141716, on insulin action in cultured adipocytes. We used translocation of glucose transporter GLUT4 to plasma membrane (PM) as a measure of insulin action. 2-AG activation of the CB1 receptor promoted insulin sensitivity whereas antagonism by SR141716 reduced insulin sensitivity. Neither drug affected GLUT4 translocation in the absence of insulin or with high doses of insulin. Consistent with these results we found that insulin-stimulated phosphorylation of the protein kinase Akt was increased by 2-AG, attenuated by SR141716, and unaffected in the absence of insulin or by addition of high-dose insulin. These data provide a functional and molecular link between the CB1 receptor and insulin sensitivity, because insulin-stimulated phosphorylation of Akt is required for GLUT4 translocation to the PM. The sensitizing effects of 2-AG were abrogated by SR141716 and Pertussis toxin, indicating that the effects are mediated by CB1 receptor. Importantly, neither 2-AG nor SR141716 alone or in combination with maximal dose of insulin had effects on GLUT4 translocation and Akt phosphorylation. These data are consistent with a model in which the endocannabinoid system sets the sensitivity of the insulin response in adipocytes rather than directly regulating the redistribution of GLUT4 or Akt phosphorylation.
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PMID:The CB1 endocannabinoid system modulates adipocyte insulin sensitivity. 1855 Nov 16

It is well established that ceramide 1-phosphate (C1P) is mitogenic and antiapoptotic, and that it is implicated in the regulation of macrophage migration. These activities require high energy levels to be available in cells. Macrophages obtain most of their energy from glucose. In this work, we demonstrate that C1P enhances glucose uptake in RAW264.7 macrophages. The major glucose transporter involved in this action was found to be GLUT 3, as determined by measuring its translocation from the cytosol to the plasma membrane. C1P-stimulated glucose uptake was blocked by selective inhibitors of phosphatidylinositol 3-kinase (PI3K) or Akt, also known as protein kinase B (PKB), and by specific siRNAs to silence the genes encoding for these kinases. C1P-stimulated glucose uptake was also inhibited by pertussis toxin (PTX) and by the siRNA that inhibited GLUT 3 expression. C1P increased the affinity of the glucose transporter for its substrate, and enhanced glucose metabolism to produce ATP. The latter action was also inhibited by PI3K- and Akt-selective inhibitors, PTX, or by specific siRNAs to inhibit GLUT 3 expression.
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PMID:Ceramide 1-phosphate stimulates glucose uptake in macrophages. 2333 42