亜鉛ヒノキチオール錯体が示す抗糖尿病作用の機構解明
2018 年 92 巻 10 号 p. 439-449
詳細
2018 年 92 巻 10 号 p. 439-449
Many zinc complexes are known to exhibit a blood glucose-lowering effect in diabetic mellitus (DM) model animals. However, the action mechanism for their anti-DM effect has not been elucidated. It has been reported that hinokitiol, which is a compound extracted from natural products, has a high safety for humans. Recently, a complex of hinokitiol with zinc, bis(hinokitiolato)zinc complex ([Zn(hkt)2]) has been shown to have a blood glucose-lowering effect. In this study, therefore, we attempted to elucidate the action mechanism for the anti-DM effect of [Zn(hkt)2]. [Zn(hkt)2] activated the insulin signaling pathway in cultured 3T3-L1 adipocytes by inducing Akt/protein kinase B (Akt) phosphorylation in an insulinindependent manner. Moreover, [Zn(hkt)2] had an inhibitory effect on protein-tyrosine phosphatase 1B (PTP1B) and phosphatase and tensin homolog (PTEN), which are the major negative regulators of the inuslin signaling pathway, in the adipocytes. [Zn(hkt)2] enhanced the phosphorylation of insulin receptor β (IRβ) or insulin receptor substrate-1 (IRS-1), each of which is situated in the upstream of Akt and is involved in the receptor-mediated insulin function, in the adipocytes with insulin, which contributes to an enhancement of insulin function. These results suggest that [Zn(hkt)2] exerts an anti-DM effect not only in an insulin-independent manner by itself, but also by an insulin receptor-mediated stimulation of insulin function in combination with insulin.
