ハットリ　フミユキ   HATTORI FUMIYUKI   服部　文幸    所属   関西医科大学  iPS・幹細胞再生医学講座    職種   研究教授
論文種別	原著(症例報告除く)
言語種別	英語
査読の有無	その他(不明)
表題	Shikonin stimulates glucose uptake in 3T3-L1 adipocytes via an insulin-independent tyrosine kinase pathway.
掲載誌名	正式名：Biochemical and biophysical research communications 略　 称：Biochem Biophys Res Commun ISSNコード：0006291X0006291X
巻・号・頁	292(3),pp.642-51
著者・共著者	Kamei Reiko, Kitagawa Yoshinori, Kadokura Michinori, Hattori Fumiyuki, Hazeki Osamu, Ebina Yousuke, Nishihara Tatsuro, Oikawa Shinzo
発行年月	2002/04
概要	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.
DOI	10.1006/bbrc.2002.6714
PMID	11922615