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S Kadota

Publications and source records attributed to S Kadota.

141 records · Page 8Linked to original sources

Peroxide(s) of vanadium: a novel and potent insulin-mimetic agent which activates the insulin receptor kinase.

The actions of insulin, vanadate (V) and hydrogen peroxide (H2O2) on IGF-II binding and insulin receptor tyrosine kinase activity were studied in rat adipocytes. Incubating adipocytes with a combination of V plus H2O2 resulted in a potent synergistic effect on both the increase in IGF-II binding and the activation of the insulin receptor kinase. Catalase, which removes H2O2, abolished this synergism if added at the time of mixing of V plus H2O2 but not if added 10 min. later, suggesting that the formation of peroxide(s) of vanadate generated a potent insulin mimicker. The data support a critical role for the insulin receptor kinase in insulin action. The novel insulin-mimetic compound, a presumed peroxide of vanadate, could prove useful for investigating insulin action and may be valuable for treating insulin resistance.

Adipose Tissue↗

Stimulation of insulin-like growth factor II receptor binding and insulin receptor kinase activity in rat adipocytes. Effects of vanadate and H2O2.

Autophosphorylation of the insulin receptor on tyrosine residues and activation of the endogenous insulin receptor kinase is postulated to be a critical step in the mechanism of action of insulin. To investigate this hypothesis, the insulin-mimicking effects of vanadate (sodium orthovanadate) and H2O2 (hydrogen peroxide) alone and in combination were examined in freshly isolated rat adipocytes. Vanadate and H2O2 stimulated the translocation of insulin-like growth factor II (IGF-II) receptors to the plasma membrane of rat adipocytes in a manner analogous to insulin. IGF-II binding was increased by maximally effective doses of vanadate (1 mM), H2O2 (1 mM), and insulin (10 ng/ml) to 172 +/- 10, 138 +/- 12, and 289 +/- 16% of control, respectively. Previously (Kadota, S., Fantus, I. G., Hersh, B., and Posner, B. I. (1986) Biochem. Biophys. Res. Commun. 138, 174-178), we showed that the combination of these concentrations of vanadate plus insulin was not more potent than insulin alone. In this study, similar results were found with H2O2 plus insulin. In contrast, the combination of vanadate plus H2O2 was synergistic, effecting an increase of IGF-II binding to 488 +/- 23% of control. Amiloride inhibited the effects of vanadate, H2O2, and insulin. Adipocyte insulin receptors purified by wheat germ agglutinin chromatography were assayed for tyrosine kinase activity using the synthetic substrate poly(Glu,Tyr) (4:1). Basal activity (no in vitro insulin) was stimulated by exposure of intact cells to vanadate, H2O2, insulin, and vanadate + H2O2 to 147.7 +/- 4.3, 178.2 +/- 43.4, 495.0 +/- 67.1, and 913.2 +/- 92.0% of control, respectively. The stimulation of tyrosine kinase activity by these agents was accounted for by the insulin receptor as the augmented activity was completely immunoprecipitated with insulin receptor antibody. In these studies, the increase in IGF-II binding correlated significantly with the activation of the insulin receptor-tyrosine kinase (r = 0.927, p less than 0.001). These data support the hypothesis that activation of the insulin receptor kinase is linked to insulin action.

Adipose Tissue↗

Okilactomycin, a novel antibiotic produced by a Streptomyces species. I. Taxonomy, fermentation, isolation and characterization.

Okilactomycin, a novel antibiotic, was isolated from the culture filtrate of a strain of actinomycetes. The producing organism, strain YP-02908L, was identified as Streptomyces griseoflavus subsp. zamamiensis subsp. nov. The antibiotic was extracted with ethyl acetate and purified by silica gel column chromatography. It was obtained as colorless prisms from a dichloromethane solution. It exhibited weak antimicrobial activity against Ehrlich ascites carcinoma in vivo. The apparent molecular formula of okilactomycin was determined as C24H32O6. It is a new member of the lactone group antibiotics.

Animals↗

Vanadate stimulation of IGF binding to rat adipocytes.

Preincubation of adipocytes with insulin (10 ng/ml) stimulated binding of IGF-II to maximal levels of 160% above controls. Vanadate also augmented IGF-II binding with an increase of 126% above controls at a concentration of 1 mM. Coincubation of vanadate (1 mM) with a maximal stimulatory dose of insulin (10 ng/ml) produced no additive effect. However, at submaximal doses of insulin (0.1 ng/ml) the effect of vanadate was additive. Amiloride, a potent inhibitor of the insulin receptor kinase, inhibited the effects of both vanadate and insulin. The data are consistent with an effect of vanadate via a similar sequence of steps to that of insulin; perhaps involving activation of the insulin receptor kinase.

Adipose Tissue↗

[Radioreceptor assay of insulin and detection of anti-insulin receptor antibody using human placenta and their clinical application].

A receptor assay system for human serum insulin and a method for detection of anti-insulin receptor antibody in human serum using human placental receptor were developed. The receptor assay system was sensitive enough to measure the fasting insulin level and not interfered by serum proteins. The method for detecting antibodies to the insulin receptor was interfered by the presences of serum insulin with a relatively high levels and anti-insulin antibodies in the direct incubation method in which serum and radioinsulin were incubated simultaneously, but the interference by anti-insulin antibody was avoided in the indirect incubation method in which the receptor incubated with serum was washed before incubation with radioinsulin. With these methods, patients with carbohydrate intolerance were investigated. The insulin levels measured with receptor assay were in exact accordance with the insulin levels measured with radioimmunoassay, and no anti-insulin receptor antibody was detected in sera from normal volunteers as well as diabetic patients. However, in three cases abnormality was observed. In the first case with hypoglycemia due to extrapancreatic tumor, a low insulin immunoreactivity and a high insulin-like activity (ILA) measured with receptor assay were observed. In considering the ILA in her serum, the presence of immunoinactive insulin-like substance with hypoglycemic action was speculated. In the second case with insulin resistant diabetes, later with hypoglycemia, a substance inhibiting the binding of radioinsulin to the placental receptor was detected. Since the substance was positive even after the adsorption of insulin with charcoal in the indirect incubation method, the presence of anti-insulin receptor antibody was speculated. In the third case with high insulin level despites with mild carbohydrate intolerance, the insulin values with radioimmunoassay and radioreceptor assay were coincident and no anti-insulin receptor antibody was detected. According to further studies using the erythrocytes receptor from this patient, a decrease of insulin receptor number was confirmed. The receptor assay system and receptor antibody detection method seems to be useful for investigating the pathogenesis of some patients with carbohydrate intolerance.

Adolescent↗

Liquid chromatography-mass spectrometry analysis of propolis.

The composition of propolis, a resinous hive product collected by honeybees from various plant sources, depends on various factors such as season and vegetation of the area. Based on standards (either isolated from Brazilian propolis or reported from propolis) including chromane, diterpenes and phenolic compounds, different Brazilian propolis were analysed by LC-MS in order to determine their chemical constituents. Dicaffeoylquinic acids were detected in almost all water extracts of Brazilian propolis, whereas diterpenes, flavonoids and prenylated phenolic compounds were found in their methanol extracts. Based on the identified chemical constituents and their biological activities, it was determined that the quality of Brazilian propolis could be directly related to the phenolic constituents. Moreover, Baccharis dracunculifolia was concluded to be an important source of Brazilian propolis. Propolis samples from Peru, China and the Netherlands were also studied.

Animals↗