Insulin-Mimetic Vanadyl (IV) Complexes as Evaluated by Both Glucose-Uptake and Inhibition of Free Fatty Acids (FFA) -Release in Isolated Rat Adipocytes
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概要
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We have recently proposed the existence of some potent vanadyl complexes with blood glucose-lowering activity in experimental diabetic animals based on the results of an in vitro FFA (free fatty acids) -release assay in isolated rat adipocytes treated with epinephrine and evidence of an in vivo blood glucose lowering effect in experimental diabetic animals. However, the FFA assay depends indirectly on the glucose-uptake of vanadyl complexes in adipocytes. It is therefore necessary to develop a more reliable in vitro glucose-uptake assay, in place of the glucose uptake method using radioactive compounds such as ^<14>C-glucose, to identify insulin-mimetic vanadyl complexes. In the present study, we proposed a combined in vitro assay by using the conventional glucose oxidase method for glucose-uptake and FFA assay in isolated rat adipocytes. Insulin, vanadyl sulfate (VOSO_4), bis (picolinato) vanadyl (VO (pa)_2), and bis (6-methylpicolinato) vanadyl (VO (6mpa)_2) complexes exhibited concentration-dependent uptake of (+) -D-glucose and inhibition of FFA release in the adipocytes treated with epinephrine. Vanadyl complexes were found to accelerate glucose-uptake at lower concentrations than VOSO_4. In vitro high insulin-mimetic activity of VO (pa)_2 and VO (6mpa)_2 were thus indicated by both glucose-uptake and FFA-release, with the insulin-mimetic activity of VO (6mpa)_2 being higher than that of VO (pa)_2, as suggested by the partition coefficient (0.330 for VO (pa)_2 and 0.595 for VO (6mpa)_2). The proposed assay provides a more reliable method than each single method for the evaluation of in vitro insulin-mimetic activity of compounds.
- 公益社団法人日本薬学会の論文
- 2004-04-01
著者
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SAKURAI Hiromu
Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University
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Sakurai Hiromu
Department Of Analytical And Bioinorganic Chemistry Kyoto Pharmaceutical University
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ADACHI Yusuke
Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University
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Adachi Yusuke
Department Of Analytical And Bioinorganic Chemistry Kyoto Pharmaceutical University
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