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)

Adenosine, via interaction with A1 adenosine receptors, increases insulin sensitivity and inhibits lipolysis in adipocytes. To investigate regulation of this system, adipocytes were incubated for up to 72 h with the nonmetabolizable adenosine receptor agonist, N6-phenylisopropyl adenosine (PIA). Adenosine receptors were measured by the binding of 125I-hydroxyphenylisopropyl adenosine to membranes. PIA down-regulated adenosine receptors, decreasing the number of binding sites with no change in affinity. Adipocytes were incubated for 48 h without or with 100 nM PIA to down-regulate the A1 receptors by approximately 60%. The cells were washed, and lipolysis and glucose transport were assessed. The ability of PIA to inhibit lipolysis was markedly attenuated in the down-regulated cells. Furthermore, the EC50 of insulin was increased approximately 3-fold in the PIA-treated cells. 125I-Insulin binding to the PIA-treated cells was unchanged, demonstrating that the decreased insulin sensitivity is not due to decreased insulin receptor binding. Pertussis toxin catalyzed ADP-ribosylation of a 41-kDa protein thought to be the alpha-subunit of Gi. This 41-kDa protein was decreased in membranes from cells treated with PIA, with a maximal 50% loss. This suggests that Gi is down-regulated and that loss of both the A1 adenosine receptor and Gi are involved in the metabolic changes observed after PIA treatment.
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PMID:Adenosine receptor down-regulation and insulin resistance following prolonged incubation of adipocytes with an A1 adenosine receptor agonist. 368 Feb 21

Alterations in rat renal glucose transport following in vivo use of Freund's adjuvant were examined. Lewis-Brown Norway rats were placed in four separate injection groups: tubular basement membrane plus adjuvant [complete Freund's adjuvant (CFA) plus pertussis]; adjuvant (CFA plus pertussis); CFA only; or pertussis only. Renal handling of glucose was assessed 14 days after a single injection. No in vivo changes were noted. No histologic differences among groups were noted. However, brush border membrane vesicles prepared from animals in groups 1, 2, and 3 showed a marked decrease in glucose uptake. Further, Michaelis-Menten kinetics demonstrated a decrease in apparent Km and Vmax for glucose in groups 1, 2, and 3. CFA alone can cause a change in brush border membrane vesicle uptake of glucose. The pathogenic mechanism behind CFA-induced transport changes remains unclear. However, studies employing CFA cannot dismiss Freund's adjuvant as "inert" and must take into account functional changes created by CFA alone.
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PMID:Alterations in rat renal glucose transport following in vivo use of Freund's adjuvant. 371 53

The present work aims to study the role of the cholinergic mechanism in the hypoglycemic action of B. pertussis vaccine in rats. The vaccine resembles insulin in that the hypoglycemia produced is mainly due to the increase conversion of glucose to glycogen in the liver and muscle. Both the hypoglycemia as well as glycogen deposition was partially blocked by atropine. On the other hand the vaccine potentiated the fall in the blood sugar and deposition of glycogen in the tissues produced by physostigmine. This suggests the possible involvement of the cholinergic system in the hypoglycemic action of the vaccine.
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PMID:Role of cholinergic mechanism in the hypoglycemic action of B. pertussis vaccine. 382 Jul 32

Pertussis vaccine consisting of inactivated whole Bordetella pertussis organisms appears to induce a biphasic response on the glucose metabolism of N:NIH mice. A heat stable component assumed to be the LPS induces a transient hyperglycaemia within 6 hours after vaccination. A heat labile component assumed to be LPF, induces a hypoglycaemia and hyperinsulinaemia 2-7 days after treatment. A purified vaccine examined in this study still showed some effects on the glucose metabolism at 3-4 days after vaccination. If hypoglycaemia contributes to the neurological side effects, incidentally observed after vaccination of infants, both LPS and LPF have to be considered to be responsible for these effects.
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PMID:A biphasic glucose and insulin response in mice after vaccination with pertussis vaccine. 390 Oct 31

We studied the effect of pertussis toxin (PT) treatment on the ability of insulin to inhibit lipolysis and to stimulate glucose oxidation in isolated rat adipocytes. In cells maximally modified by PT (100% ADP ribosylation of a 41-kdalton protein in membranes), the ability of insulin to inhibit lipolysis stimulated either by PT alone or in combination with a catecholamine was abolished. In cells wherein ADP ribosylation was submaximal (about 67% modification), a small but variable antilipolytic action of insulin could still be detected. In cells maximally modified by PT, both basal and insulin-stimulated glucose oxidation were markedly reduced (to 10-15% of control levels). However, relative to the basal oxidation level, the fold stimulation by insulin in PT-treated cells was equivalent to the fold stimulation in control cells. Nonetheless, PT treatment caused a rightward shift in the dose-response curve for insulin-stimulated glucose oxidation as well as a small reduction in insulin binding. Our results point strongly not only to a link between the inhibitory guanine nucleotide regulatory complex (Gi) and the antilipolytic action of insulin but also to a link between the Gi complex and the overall regulation of glucose metabolism in adipocytes.
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PMID:Action of insulin modulated by pertussis toxin in rat adipocytes. 390 10

Mergenhagen, Stephan E. (National Institutes of Health, Bethesda, Md.). Polysaccharide-lipid complexes from Veillonella parvula. J. Bacteriol. 90:1730-1734. 1965.-A strain of Veillonella parvula (V2) elaborates an extracellular slime when grown in a nutrient medium containing only dialyzable components. Deproteinization with chloroform-butanol of ethyl alcohol-precipitated material from the supernatant culture fluid leads to the isolation of a water-soluble lipopolysaccharide (LPS1). Another component (LPS2), showing similarity in biological and immunological properties to the endotoxic antigen (LPC) isolated from whole cells, was extracted with phenol from the insoluble emulsion remaining after chloroform-butanol extraction of slime. Analysis of polysaccharides by thin-layer chromatography demonstrated the presence of glucose and galactose in LPS1 and glucose, glucosamine, galactosamine, and a methyl pentose in LPC. LPS1 failed to give a positive epinephrine skin test after intravenous injection in rabbits and failed to kill pertussis-sensitized mice, whereas LPS2 and LPC were active in both of these bioassays. Both lipopolysaccharides (LPS1 and LPC) exhibited type-specific haptenic activity in hemagglutination tests with numerous anti-Veillonella rabbit sera. LPS1 was found in these tests to be unrelated to a heterologous strain of Veillonella possessing a related somatic antigen. These experiments reveal the presence of two chemically and immunologically distinguishable polysaccharide-lipid complexes in this strain of V. parvula.
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PMID:Polysaccharide-lipid complexes from Veillonella parvula. 585 93

Recent advances in insulin secretion indicate that pertussis toxin abolishes the inhibition by alpha 2 adrenoceptor activation of insulin release by the pancreas. Pertussis toxin adenosine diphosphate (ADP) ribosylates an inhibitory guanine nucleotide-binding protein (Ni) involved in inhibition of adenylate cyclase. The decrease in cyclic adenosine monophosphate (AMP) by epinephrine may account for its inhibition of insulin release. Insulin interaction with its receptor results in an increase in the tyrosine protein kinase activity of the receptor. Second messengers for insulin are generated, hexose transport is accelerated, and a cyclic AMP-independent protein kinase is activated that phosphorylates at serinethreonine residues. The activity of membrane-bound enzymes such as adenylate cyclase and Ca2+-Mg2+-ATPase is affected. The relative importance of these effects of insulin in its regulation of cellular metabolism remains to be established.
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PMID:Insulin secretion and action. 614 90

Pancreatic islets were maintained in culture with or without islet-activating protein (IAP), which is a new protein purified from culture medium of Bordetella pertussis. These cultured islets (IAP-treated or control) were then incubated for 30 min in IAP-free medium with various insulin secretagogues. During incubation, much more insulin was released from IAP-treated islets than control islets in response to glucose, arginine, glucagon, and sulfonylurea. IAP was effective in this regard when added to cultures at concentrations higher than 0.01 ng/ml; the effect was dependent on concentration up to 100 ng/ml. Enhanced insulin secretion was associated with accumulation of cyclic AMP when breakdown of the nucleotide was prevented by a methylxanthine. Epinephrine caused marked inhibitions, via alpha-adrenergic receptors, of glucose-induced insulin release, cyclic AMP accumulation and 45Ca uptake in control islets but did not in IAP-treated islets during incubation. None of these effects of IAP pretreatment were observed unless the medium for incubation was supplemented with Ca ions. 45Ca ion flux through the islet cell membrane was accelerated by the IAP treatment; conceivably, IAP was effective in causing sustained activation of native calcium ionophores on the membrane, which would be responsible for the enhanced insulin and cyclic AMP responses characteristic of IAP-treated islets.
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PMID:In vitro effects of islet-activating protein on cultured rat pancreatic islets. Enhancement of insulin secretion, adenosine 3':5'-monophosphate accumulation and 45Ca flux. 616 8

Islet-activating protein (IAP) is a new active substance purified from the culture medium of Bordetella pertussis. The active protein possesses a molecular weight of 77,000 and an isoelectric point of pH 7.8. The nature of IAP-action is characterized by enhancement of insulin secretory response to glucose and other stimulants. A single injection of IAP into spontaneous diabetes rats resulted in normalization of their glucose intolerance over a period of a month. Acute and chronic animal toxicity tests showed that LD50 of IAP was 127 micrograms/kg in mice and 144 micrograms/kg in rats. After these animal experiments, phase 1 studies were designed and undertaken to establish dosage, duration of action and other factors. IAP of 0.5 micrograms/kg or 1.0 micrograms/kg did not bring about any serious toxic or adverse effects in five volunteers. On the 4th day of a single injection of IAP, insulin secretory response was proved to be enhanced. Follow-up studies showed that the IAP-action continued over a month or at most two months. Two features of IAP, i.e., the enhancement of insulin secretory response and the long duration of the action, was confirmed in healthy persons as well as in animals. As expected, IAP has a strong antigenic reaction resulting in formation of IgG antibody and possibly IgE antibody. The antigenicity of IAP causes some hindrance to clinical usefulness. For avoidance of anaphylactic reaction, IAP should be given repeatedly with care. The problem concerning antigen-antibody reaction should be overcome as soon as possible before the clinical use of IAP as a medicament.
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PMID:Effects of islet-activating protein (IAP) on blood glucose and plasma insulin in healthy volunteers (phase 1 studies). 624 81

The influence of living Bordetella pertussis on the induction and duration of pathophysiological reactions in mice infected intranasally with graded doses of culture was studied. Lethally infected mice showed loss of body weight, spleen atrophy, pronounced hypothermia and hypoglycemia, and highly elevated levels of leukocytes and serum immunoreactive insulin. Sublethally infected mice showed normal weight gain, practically normal temperature, spleen enlargement, lesser pronounced hypoglycemia, lower but significantly elevated levels of leukocytes and serum immunoreactive insulin, and histamine sensitization. Intensity of each reaction was related to the degree of lung infectivity. Hypothermia and leukocytosis were highly correlated. Concentration of serum immunoreactive insulin was closely related to the level of leukocytosis but not to the level of glucose. The strain and age of mice significantly affected the degree and duration of the reactions. The results suggest that the intranasally infected mouse may provide a useful model for investigations on whooping cough.
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PMID:Bordetella pertussis respiratory tract infection in the mouse: pathophysiological responses. 624 73


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