Tannic acid inhibits insulin-stimulated lipogenesis in rat adipose tissue and insulin receptor function in vitro

Tannins occur naturally in relatively abundant amounts in fruits, herbal medicines and common beverages. Thus an understanding of how these polyphenols affect peptide hormone action is of importance. We report here that tannic acid (a hydrolysable tannin) inhibits insulin-stimulated lipogenesis in rat adipose tissue in vitro, with an IC₅₀ estimated to be about 350 M. However, its monomer, gallic acid, did not show a similar inhibitory effect at concentrations up to 1 mM. The inhibition by tannic acid was less evident with higher concentrations of bovine serum albumin in the incubation buffer. This was attributed to the formation of a tannin-protein complex between bovine serum albumin and tannic acid. In a binding assay, it was observed that the specific binding of insulin to its receptor was not inhibited by tannic acid in the concentration range 0–200 M. However, insulin-stimulated autophosphorylation of the insulin receptor, and receptor-associated tyrosine kinase phosphorylation of RR-SRC peptide, were inhibited by tannic acid at concentrations as low as 25 M. Our data do not support the current speculation that tannins affect the activity of peptide hormones by binding to them. Therefore, our finding opens up a new perspective in the understanding of the mode of action of tannins on such hormones.     

Alkaline phosphatase in human lymphocyte subpopulations

Summary The levels of membrane alkaline phosphatase have been measured on different lymphocyte fractions from human peripheral blood separated on bovine serum albumin discontinuous gradients. The peak in enzyme activity was observed in a non-T-, non-B-cell fraction, rich in null lymphocytes; the lowest values were found in the fraction with the highest proportion of T-cells.     

Serologisch-hämatologische und immunologische Untersuchungen an winterschlafenden Fledermäusen (Myotis myotis S.)

Summary Antibody deficiency in hibernating bats (Myotis myotis S.) was shown by precipitin reaction. The-globulins in serum of hibernating bats decreased to one half of the normal value. There is significant leukopenia, lymphopenia and eosinopenia. Injected bovine albumin was completely removed within 9 days in active animals, in torpid animals only 1/25 was absorbed from the 6th to the 23rd day.     

Sur l'interaction de la Protamine avec des protéines sériques

Summary We noticed the formation of a precipitate on adding salmine to dilute aqueous protein solution at pH 6–7. Human and bovine serum albumin, human -globulin, and the perchloro- and sulfosalicylosoluble mucoides do not precipitate in this condition. - and -lipoproteins prepared by floatation and by Sandor's technique gave S-shaped nephelometric titration curves, as did haptoglobin, a mixture of the types Hp II-Hp II and Hp II-Hp I. In sera incubated 24 h at 37°C with protamin, the dextran sulphate test and the cetavlon test show a diminished value for -lipo- and -glucoprotein. Lipoprotein degradation is probably enzymatic in nature.     

Der Einfluss der γ-Globuline auf die Viskosität

Summary Depending on concentration of fibrinogen, increasing concentrations of -globulines cause an exponential increase of viscosity, which is more pronounced, the higher the basic concentration of fibrinogenis. Fibrinogen that is dependent on -globulines and albumin, -globulines that is dependent on albumin, or albumin that is dependent on fibrinogen and -globulines do not show this behaviour.

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Für die zuverlässige Mitarbeit sei der biochem.-techn. Assistentin, Fräulein Ilse Stelter, gedankt.     

Hemmung der Corticosteroid-11Β-hydroxylierung durch einen Extrakt aus corpus pineale

Summary A hexane extract of bovine pineal glands reduced the production of 11-OH-corticosteroids and augmented the formation of 11-desoxycorticosteroids in slices of bovine adrenal cortex. It is suggested, therefore, that bovine pineal glands contain one or several substances which inhibit the 11-hydroxylation of corticosteroids.     

Preferential excretion of glycated albumin in C57BL-Ks-J mice: Effects of diabetes

Urinary excretion of glycated albumin was quantitated in genetically hyperglycemic mice (C57BL-Ks-J, db/db mice), a model for non-insulin-dependent diabetes mellitus, and compared with their non-diabetic littermates. The data indicated a preferential excretion of glycated albumin in non-diabetic mice. This phenomenon of editing of glycated albumin is decreased significantly in diabetic mice. Quantitative measurements of overall excretion of glycated albumin suggested that the loss of editing in diabetic mice is due to the dilution of glycated albumin by the unmodified albumin which is excreted in large amounts in diabetic mice. Therefore, the loss of editing observed in this model resembled the one we characterized in insulin-dependent diabetic humans and a streptozotocin-diabetic rat model³.     

Action des différentes formes actives de la vitamine A sur le mécanisme immunitaire chez le rat

Summary In this work, we have studied the role of different active forms of vitamin A considered as adjuvant of the immune mechanism in the rat. We also pointed out the adjuvant effect of retinol and retinal in comparison with the other active components of that vitamin with the bovine -globulin which is not an immunogenic antigen in itself in the control rat. Despite the fact that vitamin A has no antigenecity, it still possess an extrinsic adjuvanticity in presence of bovine -globulin. The degree of the immune response is increased.

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Action des différentes formes actives de la vitamine A sur le mécanisme immunitaire chez le rat

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Supporté par le C.N.R.S., Liban.     

Comparison of lysine and tryptophan catabolizing enzymes in rat and bovine tissues

Summary Earlier studies indicate that -aminoadipate aminotransferase (AadAT) and kynurenine aminotransferase (KAT) activities from rat tissues are associated with a single protein. However, our recent studies indicate that AadAT activity from bovine liver and kidney is not associated with KAT activity. To test whether the lysine and tryptophan catabolism in bovine tissues differ from that in rat tissues, we compared the activities of enzymes involved in lysine and tryptophan pathways in rat and bovine tissues. The activities of lysine catabolizing enzymes such as AadAT, lysine -ketoglutarate reductase and saccharopine dehydrogenase in the bovine tissues were significantly lower than those found in rat tissues. The activities of tryptophan catabolizing enzymes such as KAT and kynurenine hydroxylase in the bovine tissues were negligible as compared to those in rat tissues. The results suggest that lysine is degraded via the saccharopine pathway in the livers and kidneys of both species but the metabolism of tryptophan in bovine tissues may be different from that in rat tissues.Acknowledgments. This work was supported by a grant from the Children's Hospital of Michigan and by a Research Career Development Award from the National Institutes of Health to D. R. Deshmukh.     

α1-Adrenergic stimulation of ketogenesis and fatty acid oxidation is associated with inhibition of lipogenesis in rat hepatocytes

Summary The effect of norepinephrine on fatty acid synthesis (³H₂O incorporation into fatty acids), on fatty acid oxidation to CO₂ and on ketogenesis was studied in isolated hepatocytes of fed rats. After incubation with norepinephrine (50 M), lipogenesis was lower (5.7±1.1 nmoles³H₂O incorporated into fatty acids/mg dry weight/30 min) than in controls (7.5±1.7; n=6, p<0.02). In contrast, (1-¹⁴C) palmitate conversion into total ketone bodies was increased to 10.9±1.8 nmoles/mg/30 min with norepinephrine, vs 8.5±1.6 in controls (p<0.05), and more (1-¹⁴C) palmitate was converted to¹⁴CO₂ with norepinephrine than in controls (1.48±0.10 nmoles/mg/30 min vs 1.06±0.11, p<0.05). The inhibitory effect of norepinephrine on lipogenesis was abolished by addition of the ₁-receptor blocker prazosin, but not by ₂ or -blockers. The results demonstrate that the ketogenic effect of norepinephrine is coupled with an inhibitory effect on lipogenesis which may be explained by diminished activity of acetyl-CoA carboxylase, diminished formation of malonyl-CoA and decreased activity of carnitine palmitoyl transferase I.     

Die Wirkung von Eiweissfraktionen normaler menschlicher Sera auf die Thrombocytenzahl der Maus

Summary We investigated the thrombocytosis-producing activity of different protein-fractions of human sera in mice. The whole sera, the albumin,- and-globulins were ineffective, whereas the-globulins caused a more or less exact thrombocytosis in mice. The effectiveness of the thrombopoetic activity present in normal human sera is probably inhibited by a factor connected with another protein-fraction.     

The COMT inhibitor tolcapone potentiates the anticataleptic effect of Madopar in MPP+-lesioned mice

Orally administered Madopar (levodopa/benserazide 41) dose-dependently antagonized haloperidol-induced (1 mg/kg s.c.) catalepsy in MPP⁺-lesioned mice. Pretreatment with a new selective catechol-O-methyltransferase (COMT) inhibitor, tolcapone (30 mg/kg p.o.), slightly potentiated the antagonistic effect of Madopar (15 mg/kg p.o.) on haloperidol-induced catalepsy. The ability of tolcapone to increase the Madopar effect was significantly attenuated by high doses of 3-O-methyldopa (3-OMD) (800 mg/kg i.p.). This might suggest a competitive blockade of the active transport of levodopa through the blood-brain barrier. In conclusion, the inhibitory effect of tolcapone on the O-methylation of levodopa to 3-OMD by COMT is largely due to improved levodopa and dopamine availability in the brain, and to the reduced formation of 3-OMD.     

Die Unterdrückung des letalen anaphylaktischen Schocks bei der Maus

Summary The effect was investigated of Endoxan (cyclophosphamide) on anaphylactic shock in mice, induced with the aid of pertussis organisms. A complete inhibition by a dose of 4 mg/mouse can be proved. The formation of antibodies in the Endoxan-treated mice is depressed.     

Die normale Zusammensetzung des Plasmaproteinfilmes an der Oberfläche von Kaninchenerythrocyten

Summary A plasma protein film is adsorbed at the surface of the red cells of rabbit. The percentage composition of this plasma protein film is different from the protein composition of plasma.-Globulin, lipoprotein and prealbumin are increased, albumin is decreased at the surface of the red cells.     

Identification of calcium antagonist receptor binding sites using (3H)nitrendipine in bovine tracheal smooth muscle membranes

Summary (³H)Nitrendipine binding to the bovine tracheal muscle membrane at 25°C was rapid, saturable (B_max=14.8±3.9fmol/mg protein) and of high affinity (K_d=0.15±0.04 nM). The rank order of Ca²⁺ antagonists competing for airway (³H)nitrendipine binding was nitrendipine nisoldipine nifedipine » verapamil. Cromolyn, however, neither inhibited nor increased the binding.J.B.C. is a visiting associate professor at the NYMMC. We thank Ms. Pang-jang Chang for technical assistance. This work is supported by a grant (NSC 72-0412-BO10-R20) from the National Science Council, ROC. To whom reprint requests should be addressed: Allergic Disease Center, Creighton University School of Medicine, Omaha, Nebraska 68178.     

Activité antifibrillante chez l'animal d'un nouveau dérivé de la phényl-éthylamine

Summary A new synthetic phenyl-ethyl-amine derivative, the 2-[N- (3, 4-methylen-dioxyphenylethyl)-methylaminomethyl]-tetrahydrofuran, No. 11 081, exhibits a strong protective effect against cardiac fibrillation and arrhythmias produced by various experimental methods: against fibrillation due to aconitine 3 × 10^–8 on the isolated cat's heart, it is active in a concentration of 10^–6–2 × 10^–6. Against cardiac arrhythmias produced in the cat by adrenaline + CHCl₃ or cyclopropane, it shows a protective effect by 5–10 mg/kg i.v. and even perorally by 50 mg/kg. In these tests, the antifibrillatory activity of the new compound seems to be roughly the same as that of -fagarine, and higher than that of procaine.

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9^e communication sur les dérivés des alcoylène-imines; 8^e communication, cf. Exper.10, 261 (1954).     

Effect of 723-1723-1723-1on ethanol withdrawal in mice

Summary ⁹ (10 mg/kg, i.p.) administered to mice immediately after withdrawal from a 3-day exposure to ethanol vapor was found to intensify withdrawal reactions. No effect was seen when ⁹ was administered chronically during the exposure to ethanol.     

Naloxone prevents the analgesic action of α-MSH in mice

Summary -MSH (0.1, 1, 10 g) was administered intracerebroventricularly and its action on pain sensitivity was investigated by the hot-plate method in mice. -MSH produced dose-dependent analgesia and this analgesic effect was prevented by naloxone (1 mg/kg, s.c.). It is possible that -MSH may play a role in the mechanism of pain through endogeneous opioid systems.     

Inhibition of food intake in the rat by cyproheptadine

Summary In a model of conditioned feeding behavior, oral administration of cyproheptadine (1–100 mg/kg), 30 min before presentation of food, produced a dose-dependent reduction of food intake in the rat (ED₅₀17 mg/kg during the 1st h of testing). This anorexic effect persisted for at least 24 h. These results provide further evidence that under certain conditions cyproheptadine, which is used as an orectic agent in man, can produce anorexia.     

Influence of adrenergic blocking agents upon morphine and catecholamine analgesic effect

Resumen Las catecolaminas adrenalina (0,25 y 0,5 mg/kg) noradrenalina (0,5 y 1 mg/kg) e isoproterenol (4 y 8 mg/kg) producen efecto analgésico significativo en lauchas. También aumentan (adrenalina 0,25 mg/kg, noradrenalina 0,5 mg/kg e isoproterenol 4 mg/kg) el efecto analgésico de pequeñas dosis de morfina (1 mg/kg). El bloqueador -adrenérgico dihidroergotamina (4 mg/kg) no influencia substancialmente estas acciones, pero el bloquente-adrenérgico propranolol (1 mg/kg) bloquea los efectos analgésicos de la morfina, adrenalina e isoproterenol, no siendo tan efectivo contra la noradrenalina. Se deduce que debe existir un compromiso de receptores-adrenérgicos en el mecanismo de los efectos analgésicos de las catecolaminas y también de la morfina.

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Fellow of the Consejo de Investigaciones Cientificas y Técnicas.