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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin treatment of platelets is associated with increased prostaglandin E1-stimulated adenylyl cyclase activity and decreased platelet aggregation. Because non-insulin dependent (Type II) diabetes mellitus is associated with hyperinsulinemia, we sought to determine the effect of insulin treatment in vivo and in vitro upon stimulation of platelet adenylyl cyclase by prostaglandin E1. Incubation of platelet-rich plasma obtained from normal subjects with 2 microM prostaglandin E1 resulted in a 16-fold increase in cAMP accumulation. Pre-incubation of platelet-rich plasma with 0.7 nM insulin resulted in a 62% increase in prostaglandin E1 (2 microM)-stimulated cAMP accumulation (p < 0.005). Pretreatment of platelets with cholera toxin prior to incubation with insulin had no effect on subsequent prostaglandin E1-stimulated cAMP accumulation. By contrast, pretreatment of platelets with pertussis toxin prior to incubation with insulin resulted in a nearly 2-fold increase in prostaglandin E1-stimulated cAMP accumulation (p < 0.005). To determine whether platelets exposed in vivo to elevated concentrations of insulin would show similar responses, we isolated platelet-rich plasma from subjects before and after a 120 minute euglycemic clamp study in which insulin was infused (40 mU m-2min-1) intravenously. Patients who underwent the euglycemic clamp study achieved steady state serum levels on insulin of 0.70 +/- 0.19 pmol/ml. Platelets obtained after insulin infusion had a 65% increase in prostaglandin E1-stimulated cAMP. Our results indicate that serum levels of insulin that are common in patients with type II diabetes mellitus can increase the sensitivity of platelet adenylyl cyclase to stimulation by prostaglandin E1.
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PMID:The effects of in vitro and in vivo exposure to insulin upon prostaglandin E1 stimulation of platelet adenylate cyclase activity in healthy subjects. 764 95

Pertussis toxin was used to block insulin-stimulated phosphatidylinositol (PI)-glycan hydrolysis, consequent de novo synthesis of phosphatidic acid (PA) and the diacylglycerol (DAG) production that results from these two related processes in BC3H-1 myocytes. In contrast, pertussis toxin pretreatment did not inhibit insulin-stimulated hydrolysis of phosphatidylcholine (PC) which was found to be at least partly due to activation of a phospholipase D. Moreover, pertussis toxin-insensitive PC hydrolysis was accompanied by rapid biphasic increases in DAG and translocative activation of protein kinase C (PKC). Insulin-stimulated glucose transport was also insensitive to pertussis toxin pretreatment. Our findings suggest that insulin-stimulated PC hydrolysis pays an important role in DAG/PKC signalling during insulin action.
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PMID:Insulin-stimulated phosphatidylcholine hydrolysis, diacylglycerol/protein kinase C signalling, and hexose transport in pertussis toxin-treated BC3H-1 myocytes. 785 72

Insulin/dexamethasone/methylisobutylxanthine (hormones/IBMX) induce 3T3-L1 fibroblasts to differentiate into adipocytes. Our previous study suggested that pertussis toxin (IAP)-sensitive GTP-binding protein(s) (G-protein) is involved in the process of differentiation by hormones/IBMX, accompanied by c-fos induction. Northern blotting indicated that among the IAP-sensitive G-proteins, the levels of Gi2 alpha, Go alpha, and Gi3 alpha mRNA were decreased, increased and unchanged, respectively. Gi1 alpha was undetectable and IAP attenuated the decrease in Gi2 alpha mRNA level but did not affect the change in Go alpha mRNA level during the adipocyte differentiation. These results indicate that IAP-sensitive Gi2 alpha mRNA level is decreased during adipocyte differentiation. A combination of phosphatidylinositol-specific phospholipase C (PI-PLC) and IBMX induced c-fos expression in 3T3-L1 fibroblasts similar to that induced with hormones/IBMX. c-fos induced by both stimulators was also diminished by anti-inositolglycan antibody or anti-PI-PLC antiserum. Insulin stimulated the release of inositolproteoglycan and diacylglycerol from 3T3-L1 fibroblasts, which was suppressed by IAP treatment. These findings suggested that one of the pathways of adipocyte differentiation induced by hormones/IBMX occurs via the inositolglycan-specific PI-PLC cascade coupled to IAP-sensitive G-protein(s). Both activation of glycerophosphate dehydrogenase and stimulation of insulin-dependent 2-deoxyglucose uptake induced by hormones/IBMX were enhanced in protein kinase C-depleted cells exposed to phorbol 12-myristate 13-acetate (PMA), and attenuated in IAP-treated cells. The level of a 32P-labeled 52 kDa protein in plasma membrane fractions immunoprecipitated by anti-PI-PLC antiserum was increased by PMA stimulation, abolished in PMA-treated cells, and increased in IAP-treated cells. These findings suggest that protein kinase C phosphorylates PI-PLC, resulting in a decrease in PI-PLC activity related to the signal transduction pathway of adipocyte differentiation of 3T3-L1 fibroblasts.
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PMID:Possible involvement of phosphatidylinositol-specific phospholipase C related to pertussis toxin-sensitive GTP-binding proteins during adipocyte differentiation of 3T3-L1 fibroblasts: negative regulation of protein kinase C. 798 Dec 46

In the present work we have investigated the effects of several growth factors on the expression of Angiotensin II (A-II) receptors subtype AT1 and their pertussis toxin-insensitive coupling to G-proteins in bovine adrenal fasciculata-reticularis cells (BAC). Insulin, Insulin-like growth factor and basic Fibroblast growth factor increased AT1 receptors (mRNA and binding sites) as well as the alpha subunit of Gq (mRNA and protein) and G11 (protein). These changes were associated with an enhanced A-II-induced inositol phosphate accumulation and cortisol production. In contrast, Transforming growth factor beta 1, which reduced slightly AT1 binding sites, but not the level of alpha q or alpha 11 proteins, did not change the A-II-induced inositol phosphate accumulation. However, this factor, as previously reported, markedly reduced cortisol production.
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PMID:Regulation by growth factors of angiotensin II type-1 receptor and the alpha subunit of Gq and G11 in bovine adrenal cells. 801 89

A novel pathway for physiological "cross-talk" between the insulin receptor and the regulatory Gi-protein has been demonstrated. We tested the hypothesis that a coupling defect between Gi and the insulin receptor is present in the liver of obese patients with and without type II diabetes. Insulin 1 x 10(-9) M (approximately ED50) and 1 x 10(-7) M (Max) inhibited pertussis toxin-catalyzed ADP ribosylation of Gi in human liver plasma membranes from lean and obese nondiabetic patients. However, 1 x 10(-7) M insulin was without effect in membranes from patients with type II diabetes. This coupling defect was not intrinsic to Gi, since Mg2+ and GTP gamma S inhibited pertussis toxin-catalyzed ADP ribosylation in both diabetic and nondiabetic patients. Binding of insulin of the alpha-subunit and activation of the tyrosine kinase intrinsic to the beta-subunit of the insulin receptor are not responsible for the coupling defect. 125I insulin binding is the same in obese patients with or without diabetes. Tyrosine kinase of the insulin receptor is decreased in diabetes. However, a monoclonal antibody to the insulin receptor (MA-20) at equimolar concentrations with insulin equally inhibits pertussis toxin-catalyzed ADP ribosylation of Gi without activating tyrosine kinase or insulin receptor autophosphorylation. Immunodetection of G-proteins suggested that Gi3 alpha was normal in diabetes and Gi1-2 alpha was decreased by 40% in the diabetic group as compared to the obese nondiabetic group but was normal when compared to the lean non diabetic group. We conclude that the novel pathway of insulin signaling involving the regulatory Gi proteins via biochemical mechanisms not directly involving the tyrosine kinase of the insulin receptor is altered in obese type II diabetes and offers a new target for the search of the mechanism(s) of insulin resistance.
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PMID:Guanine nucleotide binding regulatory proteins in liver from obese humans with and without type II diabetes: evidence for altered "cross-talk" between the insulin receptor and Gi-proteins. 820 Sep 11

Insulin has a paradoxical effect on a 41kDa Gi-like protein: Although insulin-treatment of rat adipocytes inhibited pertussis toxin-catalyzed ADP-ribosylation of a 41kDa G-protein in membranes in a dose-dependent manner, it simultaneously increased ADP-ribosylation of a 41kDa G-protein that co-immunoprecipitates with the insulin receptor (GIR41). The latter effect was insulin concentration- and time-dependent. The dose-dependent stimulatory effect of insulin on the autophosphorylation of the insulin receptor and on the ADP-ribosylation of the GIR41 in the insulin receptor immunoprecipitates closely paralleled each other. The time course of insulin-stimulated increase in the ADP-ribosylated GIR41, although rapid, was slower than the autophosphorylation of the receptor. The GIR41 is associated with and regulated by the insulin receptor further supporting an important role for this G-protein in modulating insulin action at the receptor level.
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PMID:Insulin stimulates association of a 41kDa G-protein (GIR41) with the insulin receptor. 821 41

Physiologically, the action of insulin on carbohydrate and lipid metabolism is opposed by several hormones, including glucocorticoids, glucagon, catecholamines, and pituitary GH. Perhaps least is known about the mechanism(s) involved in the antiinsulin action of GH. Since the generation of diacylglycerol (DAG) appears to be an early event in the insulin-signaling cascade, it was of interest to determine whether GH would interfere with this effect of insulin. Experiments were conducted to determine whether insulin would stimulate the generation of DAG in adipocytes of the obese (ob/ob) mouse, and whether this response could be blocked by the diabetogenic GH derivative S-carboxymethylated human GH (RCM-hGH). Isolated adipocytes of the ob/ob mouse were used for these studies, because unlike normal rodents, the ob/ob mouse responds predictably to the antiinsulin action of GH. Insulin produced a rapid biphasic increase in the amount of DAG in a crude membrane fraction of the adipocytes. The first peak in DAG mass occurred within 5 min of exposure of the cells to insulin, and the second peak occurred after 30 min. The first peak in DAG mass did not occur in adipocytes that had been incubated with pertussis toxin before exposure to insulin. Also, adipocytes isolated from ob/ob mice that had been treated with RCM-hGH failed to respond to insulin with an increase in DAG mass. RCM-hGH blocked both the first and second insulin-induced peaks in DAG mass within 6 h of its administration. This is the time at which ob/ob mouse adipocytes exhibit increased insulin resistance in response to RCM-hGH. Neither exposure to insulin nor treatment with RCM-hGH had any appreciable effect on the fatty acid composition of the DAG present in the adipocyte membranes. These findings are compatible with the idea that GH produces some defect in the insulin-signaling cascade that is proximal to the events that result in the generation of DAG in the adipocyte.
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PMID:The stimulatory effect of insulin on diacylglycerol generation in adipocyte membranes from ob/ob mice is impaired by growth hormone. 846 67

Several groups have shown a relationship between the insulin receptor and inhibitory G proteins, G(i). An antisera, 8729, to a peptide sequence (KNNLKDCGLF) corresponding to the carboxyl termini of G(i)alpha subunits was used to investigate this relationship by immunoelectron microscopy. Rat adipocytes were incubated in the absence or presence of 100 ng/ml insulin for 1 h and fixed for immunoelectron microscopy. Insulin-treated adipocytes stained with 8729 were labeled at the cell surface at a much higher density than control adipocytes. Subcellular fractionation of insulin-treated and control cells was followed by PAGE and Western blots of the plasma membrane and low-density microsomes with 8729. The density of the bands did not change in response to insulin treatment. Antibodies to noncarboxyl terminus sequences of the alpha subunit were used for immunoelectron microscopy and no difference was noted between insulin-treated and control adipocytes. These results indicated that 8729 was detecting a conformational change in the structure of G(i)alpha subunit in the plasma membrane in response to insulin. This unmasking of the carboxyl terminus was also seen in response to treatment with phenylisopropyladenosine and prostaglandin E2. Pertussis toxin-catalyzed ADP ribosylation also unmasked the carboxyl terminus. In contrast, isoproterenol, an agonist of stimulatory G proteins (Gs), did not induce an unmasking of the carboxyl terminus. These results support the hypothesis that some of insulin's effects are mediated through G(i) proteins in adipocytes.
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PMID:Insulin induces an unmasking of the carboxyl terminus of G(i) proteins in rat adipocytes. 848 58

Tyrosine kinases are involved in cell signalling of growth factors such as insulin and insulin-like growth factor (IGF-I) and others. Insulin and IGF-I receptors which possibly feedback on insulin release are established in insulin-secreting cells. The role of tyrosine kinase in insulin secretion is controversial. Both the tyrosine kinase inhibitors tyrphostin 25 (TYR) and genistein (GEN), but not its structurally similar albeit biologically inactive analogue daidzein, increase insulin release at 16.7 mM glucose in INS-1 cells, an insulin secreting cell line. Tyrosine kinase activity is inhibited by GEN, but not diadzein. The inhibitory effects of either insulin or IGF-I on insulin release are abolished by 10(-4) M GEN but not by daidzein indicating an involvement of tyrosine kinase in the inhibitory effect of both insulin and IGF-I on insulin release. Since GEN was argued not to be specific for tyrosine kinase, several second messengers were investigated. cAMP is not influenced. The insulinotropic effect of acutely administered TPA is not influenced by GEN while in protein kinase C (PKC)-downregulated cells the insulinotropic effect of GEN is preserved: both indicate no involvement of PKC in GEN effect. Since pertussis toxin (PT) pretreatment has no effect on the inhibitory effects of IGF-I on insulin release, a PT-sensitive G-protein is not likely to be involved. The data indicate that tyrosine kinase is involved in the inhibitory effects of insulin and IGF on insulin release in INS-1 cells, possibly mediating the negative feedback effect.
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PMID:Role of tyrosine kinase in insulin release in an insulin secreting cell line (INS-1). 856 11

Adrenaline and somatostatin inhibit insulin secretion via pertussis toxin (PTX)-sensitive mechanisms. Since glucose-stimulated release involves inhibition of ATP-sensitive K+ (K+ATP) channels and activation of Ca2+ influx, we took advantage of the glucose-sensitive, insulin-secreting cell line INS-1 to investigate whether inhibitors of insulin release modulate membrane voltage and K+ATP channel activity in cell-attached patch-clamp experiments. We found that adrenaline, through alpha2-adrenoceptors, and somatostatin counteracted glucose-induced depolarization and action potentials. As expected, these effects were mediated via PTX-sensitive G proteins since PTX pretreatment of the cells eliminated the effects of adrenaline and somatostatin on membrane voltage. When INS-1 cells were activated by adding both the K+ATP channel inhibitor tolbutamide and the adenylyl cyclase activator forskolin, adrenaline and somatostatin still repolarized the plasma membrane. Single-channel measurements in the cell-attached mode revealed that tolbutamide closed a 40 to 70 pS K+ channel which was neither reopened by adrenaline nor by somatostatin. In parallel cell preparations, insulin secretion was measured by radioimmunoassay. Insulin release induced by glucose, forskolin and tolbutamide was abolished by adrenaline. In contrast, somatostatin attenuated insulin secretion by only 30%. After comparing the potency of adrenaline and somatostatin on membrane voltage and on insulin secretion, it is concluded that the repolarizing effect of adrenaline on membrane voltage is not sufficient to explain its potent inhibitory effect on insulin secretion.
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PMID:Adrenaline-, not somatostatin-induced hyperpolarization is accompanied by a sustained inhibition of insulin secretion in INS-1 cells. Activation of sulphonylurea K+ATP channels is not involved. 866 72


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