徳島大学 教育・研究者情報データベース(EDB)

1. (英) Kamei Reiko

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2. (英) Kitagawa Yoshinori

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3. (英) Kadokura Michinori

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4. (英) Hattori Fumiaki

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5. (英) Hazeki Osamu

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6. 蛯名 洋介

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7. (英) Nishihara Tatsuro

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8. (英) Oikawa Shinzo

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(英) Shikonin stimulates glucose uptake in 3T3-L1 adipocytes via an insulin-independent tyrosine kinase pathway.

(英) Type 2 diabetes is due to defects in both insulin action and secretion. In an attempt to discover small molecules that stimulate glucose uptake, similar to insulin, a cell-based glucose uptake screening assay was performed using 3T3-L1 adipocytes. Shikonin, a substance originally isolated from the root of the Chinese plant that has been used as an ointment for wound healing, was thus identified. Shikonin stimulated glucose uptake and potentiated insulin-stimulated glucose uptake in a concentration-dependent manner in 3T3-L1 adipocytes. Stimulation of glucose uptake was also observed in rat primary adipocytes and cardiomyocytes. Like insulin, shikonin-stimulated glucose uptake was inhibited by genistein, a tyrosine kinase inhibitor, and enhanced by vanadate, a tyrosine phosphatase inhibitor. However, in contrast to insulin, shikonin-stimulated glucose uptake was not strongly inhibited by wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K). In vitro phosphorylation analyses revealed that shikonin did not induce tyrosine phosphorylation of the insulin receptor, but significantly induced both Thr-308 and Ser-473 phosphorylation of Akt. Our results suggest that in 3T3-L1 adipocytes, shikonin action is not mediated primarily via the insulin receptor/PI3K pathway, but rather via another distinct tyrosine kinase-dependent pathway leading to glucose uptake involving Akt phosphorylation.

1. (英) 3T3 Cells
2. (英) Adipocytes
3. (英) Androstadienes
4. (英) Animals
5. (英) Anti-Inflammatory Agents, Non-Steroidal
6. (英) Biological Transport
7. (英) Drugs, Chinese Herbal
8. (英) Enzyme Inhibitors
9. (英) Genistein
10. グルコース(glucose)
11. (英) Glucose Transporter Type 4
12. (英) Humans
13. インスリン(insulin)
14. (英) Male
15. (英) Medicine, Chinese Traditional
16. (英) Mice
17. 分子構造(molecular structure)
18. (英) Monosaccharide Transport Proteins
19. (英) Muscle Proteins
20. 心筋(myocardium)
21. (英) Naphthoquinones
22. リン酸化(phosphorylation)
23. (英) Protein-Serine-Threonine Kinases
24. (英) Protein-Tyrosine Kinases
25. (英) Proto-Oncogene Proteins
26. (英) Proto-Oncogene Proteins c-akt
27. (英) Rats
28. (英) Rats, Sprague-Dawley
29. (英) Receptor, Insulin
30. シグナル伝達(signal transduction)
31. (英) Vanadates

1. (英) Article.Affiliation: Suntory Biomedical Research Limited, 1-1-1 Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-8503, Japan.

2. (英) Article.PublicationTypeList.PublicationType: Journal Article