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)

We have previously suggested that at least two different G-proteins are involved in mediating insulin receptor functions. Here we identify and partially purify two G-proteins with apparent molecular masses of 41 and 67 kilodaltons (kDa) that interact with insulin receptors in rat adipocytes and human placenta. Treatment of isolated rat adipocytes with insulin inhibited pertussis toxin-catalyzed ADP-ribosylation of a 41-kDa G-protein in subsequently isolated plasma membranes by 30.2 +/- 3.0% and in partially purified insulin receptor preparations by 35.6 +/- 5.7%. There was no associated decrease in the concentration of the 41-kDa G-protein in the plasma membranes, as determined by immunoblot with a common G alpha antibody. The common G alpha antibody also recognized a 67-kDa protein in the plasma membranes, the concentration of which was not affected by insulin. However, the 67-kDa protein was enriched in partially purified solubilized insulin receptor preparations. Two similar, 41- and 67-kDa G-proteins were identified in the wheat germ-purified insulin receptor preparations obtained from human placenta. Removal of these two G-proteins from insulin receptor preparations results in loss of the ability of insulin to stimulate receptor kinase activity. Addition of a fraction enriched with 41- and 67-kDa G-proteins to the G-protein-depleted insulin receptor restores the insulin sensitivity of the insulin receptor kinase activity. Furthermore, addition of G-protein-depleted insulin receptors to the fraction containing partially purified 41- and 67-kDa G-proteins enhances pertussis toxin-catalyzed ADP-ribosylation of the 41-kDa G-protein. These results indicate that either the 41- or 67-kDa G-protein, or both, interact with the insulin receptor mediating insulin receptor kinase activity. Such mutual interaction and regulation between the insulin receptor and G-proteins could be an important component of the signal transduction mechanism for insulin.
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PMID:Identification, partial purification, and characterization of two guanosine triphosphate-binding proteins associated with insulin receptors. 144 23

Inhibition of insulin secretion from rat islets of Langerhans is known to involve at least one pertussis toxin-sensitive guanine-nucleotide binding (G) protein. We have used antisera raised against unique antigenic determinants of different members of the family of pertussis toxin-sensitive G proteins to identify these proteins in rat islets. Antiserum SG1, which recognizes both Gi1 and Gi2, reacted with an islet protein having an approximate Mr of 40,000. Antiserum I1C (Gi1 specific) failed to recognize any islet proteins, suggesting that Gi2 is present in much greater amounts than Gi1. Indeed, Gi1 levels were below the detection limit of a sensitive immunogold/silver-staining method, indicating that it may be absent from the cells of rat islets. Two different antisera were used to identify Go-like G proteins in rat islet homogenates. Both antisera reacted with a protein band which, under appropriate conditions, could be resolved to reveal two separate proteins of Mr 39-40,000. Thus, at least two molecular forms of Go are present in rat islets. Subcellular fractionation indicated that all three G proteins identified in this study (Gi2 and two forms of Go) are localized to islet membranes. No immunoreactivity could be detected in the cytosolic fraction.
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PMID:Immunological characterization of the guanine-nucleotide binding proteins Gi and Go in rat islets of Langerhans. 151 16

A brief exposure of pancreatic islets to the cytokine interleukin-1 beta (IL-1 beta) induces an initial stimulatory phase, which is followed by inhibition of islet function and eventually beta-cell damage. In the present study we have investigated the effects of IRAP, a blocker of type I IL-1 receptor and actinomycin D, an inhibitor of DNA transcription, on both the stimulatory and inhibitory effects of IL-1 beta on rat pancreatic islets in vitro. The two test agents counteracted the initial stimulatory actions of IL-1 beta on both islet glucose-induced insulin release and glucose oxidation rates. Furthermore, cycloheximide, an inhibitor of protein synthesis, could also prevent the early IL-1 beta-induced stimulation of insulin release. When islets were exposed for 1 hr to IL-1 beta and studied after 12 hr, there was a 75% inhibition of glucose induced insulin release, a 50% decrease in glucose oxidation rates and a 30% decrease in (pro)insulin biosynthesis. These effects were completely counteracted by coincubation with IRAP or actinomycin D, but were not affected by coincubation with pertussis toxin. Islet exposure to IL-1 alpha also induced a 60-80% inhibition of glucose-induced insulin release after 12 hr. As observed with rIL-1 beta, IRAP was also able to block the suppressive effects of IL-1 alpha on islet function. Mouse islets exposed for 2 hr to IL-1 beta and studied after 12 hr presented a 50% decrease in the glucose-induced insulin release. This effect was completely blocked by coincubation with a rat monoclonal antibody generated against the type I mouse IL-1 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of receptor binding and gene transcription for both the stimulatory and inhibitory effects of interleukin-1 in pancreatic beta-cells. 153 17

To examine whether glucose has regulatory effects on the expression of Gi-proteins, BC3H-1 myocytes were incubated for 24 hr in the presence of various concentrations of glucose (0-25 mM) and the amount of Gi-proteins was detected by pertussis toxin ADP-ribosylation and immunoblot analysis. Both detection methods showed a progressive decrease in the amount of Gi proteins in cells treated with increasing concentrations of glucose. A maximal reduction of 40% was observed after a 24 hr exposure to 25 mM glucose. The reduction in Gi-proteins correlated with a decrease in insulin-stimulated glucose transport.
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PMID:Glucose regulates the expression of Gi-proteins in cultured BC3H-1 myocytes. 154 Jan 64

Streptozotocin-induced diabetes is accompanied by an increase in insulin-like immunoreactivity concentration in rat submandibular salivary glands. In this study we have examined whether, in normal state, maturation is accompanied by changes in insulin-like immunoreactivity concentration of rat submandibular salivary glands. Insulin-like immunoreactivity concentrations of submandibular salivary glands were significantly higher in 11 months old rats compared with 3.5 months old control animals. A pertussis toxin pretreatment provoked an increase in insulin-like immunoreactivity, suggesting that a pertussis toxin sensitive G-protein is involved in the regulation of insulin-like immunoreactivity in the rat submandibular salivary glands.
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PMID:Maturation and insulin-like immunoreactivity in rat submandibular salivary glands: possible implication of G regulatory proteins. 157 59

Pancreatic islets stimulated with D-glucose are known to liberate arachidonic acid from membrane phospholipids and release prostaglandin E2 (PGE2). A component of the eicosanoid release induced by D-glucose has been demonstrated to occur without calcium influx and must be triggered by other coupling mechanisms. In this study, we have attempted to identify mechanisms other than calcium influx which might couple D-glucose stimulation to hydrolysis of arachidonate from membrane phospholipids in islet cells. We have found that occupancy of the beta cell plasma membrane D-glucose transporter is insufficient and that D-glucose metabolism is required to induce islet PGE2 release because 3-O-methylglucose fails to induce and mannoheptulose prevents PGE2 release otherwise induced by 17 mM D-glucose. The carbohydrate insulin secretagogues mannose and D-glyceraldehyde have also been found to induce islet PGE2 release, but the non-secretagogue carbohydrates L-glucose and lactate do not. Carbohydrate secretagogues are known to be metabolized to yield ATP and induce depolarization of the beta cell plasma membrane. We have found that depolarization by 40 mM KCl induces PGE2 release only in the presence and not in the absence of extracellular calcium, but exogenous ATP induces islet PGE2 release with or without extracellular calcium. Carbachol is demonstrated here to interact synergistically with increasing concentrations of glucose to amplify PGE2 release and insulin secretion. Pertussis toxin treatment is shown here not to prevent PGE2 release induced by glucose or carbachol but to increase the basal rate of PGE2 release and the islet cyclic AMP content. Theophylline (10 mM) exerts similar effects. Eicosanoid release in pancreatic islets can thus be activated by multiple pathways including muscarinic receptor occupancy, calcium influx, increasing cAMP content, and a metabolic signal derived from nutrient secretagogues, such as ATP.
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PMID:Arachidonic acid metabolism in isolated pancreatic islets. VI. Carbohydrate insulin secretagogues must be metabolized to induce eicosanoid release. 159 16

Changes in cytosolic calcium concentration ([Ca2+]i) in response to extracellular calcium and epinephrine were monitored in individual rat adipocytes by both photon counting and digital imaging techniques utilizing the intracellular fluorescent calcium probes Fura-2 and Indo-1. Adipocytes containing Fura-2 were attached to coverslips and shown to be as hormonally responsive to insulin as adipocytes in suspension [3.5 +/- 0.8 (n = 5) vs. 4.2 +/- 0.6 (n = 8)-fold increase in glucose oxidation over basal in response to 0.7 nM insulin]. Basal [Ca2+]i in single rat adipocytes was found to be 128 +/- 6 nM (n = 100). The addition of either extracellular calcium or epinephrine elicited transient, concentration-dependent increases in [Ca2+]i. Although the characteristics of calcium- and epinephrine-induced calcium transients are generally similar, the peak [Ca2+]i increase over basal is higher in response to calcium vs. epinephrine [37 and 64% (1 and 27 microM epinephrine), vs. 132 and 236% (2 and 4 mM calcium)]. All the cells tested responded to calcium but only 67% responded to epinephrine. Both alpha- and beta-adrenergic agonists were able to increase [Ca2+]i. The epinephrine-induced [Ca2+]i transients appear to be dependent upon extra-cellular calcium. Neither cholera nor pertussis toxin treatments altered basal [Ca2+]i. However, after treatment of adipocytes with either pertussis or cholera toxin, epinephrine stimulated oscillations in [Ca2+]i. Digital imaging revealed that adipocytes demonstrate a high degree of intracellular spatial heterogeneity and intercellular variability in the magnitude of response to both calcium and epinephrine. These studies demonstrate the feasibility of using single rat adipocytes to monitor intracellular free calcium, using both photon counting and digital imaging.
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PMID:The effects of extracellular calcium and epinephrine on cytosolic-free calcium in single rat adipocytes. 159 65

The first steps in insulin action are binding of insulin to its receptor and activation of the insulin receptor kinase. As there is indirect evidence that further signal transduction might involve a guanine-nucleotide-binding protein (G-protein), we studied whether insulin modulates GTP binding to plasma membrane proteins of fat cells and skeletal muscle. We found that insulin rapidly increased (30 s) binding of guanosine 5'-[gamma-thio]triphosphate (GTP[S]) in a dose dependent manner (0.03-2.0 nM). This effect was not altered by pertussis toxin, but it was abolished by cholera toxin treatment of fat cells. Scatchard analysis of the binding data showed that the increased GTP[S] binding is due to a decrease in the Kd for GTP from 100 nM to 50 nM. Furthermore, binding of GTP to these plasma membranes inhibited both the binding of 125I-insulin to the insulin receptor and the stimulation of the insulin receptor kinase, suggesting a feedback interaction between the insulin-stimulated GTP-binding site and the insulin receptor. In order to identify this insulin-stimulated GTP-binding site, plasma membranes were labelled with the photoreactive GTP analogue [alpha-32P]GTP gamma-azidoanilide. We found that insulin selectively stimulated GTP binding to a 40 kDa protein. In conclusion, in plasma membranes of fat cells and skeletal muscle, the insulin receptor interacts with a 40 kDa GTP-binding site. We speculate that this 40 kDa GTP-binding site might be a G-protein which is involved in insulin signal transmission.
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PMID:Insulin activates GTP binding to a 40 kDa protein in fat cells. 164 24

Noradrenaline inhibits in rat islets the stimulation of insulin secretion induced by glucose and its potentiation by palmitate, but the signalling system responsible remains unknown. We have tested the hypothesis that noradrenaline-induced inhibition is mediated by an elevation of cyclic GMP (cGMP) levels. The analogue 8-Br-cGMP decreases dose-dependently the potentiation by palmitate of glucose-induced insulin secretion, whereas it only slightly affects the proper effect of glucose. Similarly, it abolishes palmitate acceleration of glucose-induced 45Ca2+ uptake without modifying the sugar effect. Finally, 8-Br-cGMP completely inhibits the stimulation of the lipid synthesis de novo induced by palmitate, but not that caused by glucose alone. On the other hand, noradrenaline increases dose-dependently islet cGMP content, with alpha 2-adrenergic specificity. As noradrenaline-induced elevation of cGMP is sensitive to pertussis toxin, it probably results from alpha 2-adrenoceptor activation of islet guanylate cyclase through a guanine nucleotide regulatory protein. It is concluded that the elevated cGMP levels mediate noradrenaline inhibition of lipid synthesis de novo, and hence of acceleration by palmitate of 45Ca2+ uptake and insulin secretion in the presence of glucose.
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PMID:Does cyclic guanosine monophosphate mediate noradrenaline-induced inhibition of islet insulin secretion stimulated by glucose and palmitate? 165 40

The early alterations of G-protein-dependent transductional mechanisms have been characterized in the retina of alloxan-treated diabetic rats. Five weeks after alloxan injection, pertussis toxin radiolabeling of Gi/Go proteins was markedly reduced in the retina of diabetic animals, suggesting either a reduced expression and/or the presence of some structural modification of these G-protein subtypes. The functional activity of Gs proteins, measured as stimulation of membrane adenylate cyclase by dopamine, did not seem to be impaired at this stage of the pathology; basal adenylate cyclase activity was indeed increased in diabetic rats, consistent with the observed reduction of Gi/Go inhibitory proteins. Such functional alterations of the cAMP producing system were causally related to diabetes induction, since they were reversed by treatment of diabetic animals with insulin. These results suggest that G-protein dependent transduction mechanisms are altered in the retina of diabetic animals, and that a defect of Gi/Go proteins could represent an early transductional damage in the development of diabetic retinopathy.
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PMID:Early alterations of Gi/Go protein-dependent transductional processes in the retina of diabetic animals. 165 57


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