A New Insulin-mimetic Vanadyl Complex, (N-Pyridylmethylaspartate)oxovanadium(IV) with VO(N2O2) Coordination Mode, and Evaluation of its Effect on Uptake of D-Glucose by Ehrlich Ascites Tumour Cells

Author:

Tawa Riichi1,Uchida Keiko1,Taniyama Junko1,Fujisawa Yae1,Fujimoto Seiki1,Nagaoka Takashi2,Kanamori Kan2,Sakurai Hiromu1

Affiliation:

1. Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Nakauchi-cho 5, Yamashina-ku, Kyoto 607-8414, Japan

2. Department of Chemistry, Faculty of Science, Toyama University, Gofuku-cho 3190, Toyama 930-0888, Japan

Abstract

Abstract Because it has been confirmed that the vanadyl(IV) ion and its complexes act as insulin mimetics, a new organic vanadyl complex, (N-pyridylmethylaspartate)oxovanadium (VOPASP) with VO(N2O2) coordination mode, was prepared. Development of a simple and rapid in-vitro assay is needed for recognition of potent insulin-mimetic complexes. Treatment of Ehrlich ascites tumour cells with 2-deoxyglucose in the presence of vanadyl sulphate, or other vanadyl complexes with the same coordination mode (VOPASP, bis(picolinate)oxovanadium (VOPA) and bis(6-methyl picolinate)oxovanadium (VOMPA)), in the presence of 2-deoxy-D-[1-3H]glucose ([3H]deoxyglucose), resulted in concentration-dependent uptake of 2-deoxyglucose by the cells. The responses of the cells to the vanadyl complexes were reflected, in part, by results obtained from the free fatty acid-releasing assay using rat adipocytes. These results show that the in-vitro assay with Ehrlich ascites tumour cells provides an accurate and rapid assessment of glucose uptake by the cells. The assay is proposed as a means of predicting the insulin-mimetic activity of the vanadyl complexes and for studying the mechanism of action of the complexes.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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