Abstract
To determine the effects and the underlying mechanism of diosgenin (DSG) and 5-methoxypsoralen (5-MOP), two main active components in the classical Chinese prescription Hu-Lu-Ba-Wan (HLBW), on insulin resistance, HepG2 cells were incubated in medium containing insulin. Treatments with DSG, 5-MOP, and their combination were performed, respectively. The result showed that the incubation of HepG2 cells with high concentration insulin markedly decreased glucose consumption and glycogen synthesis. However, treatment with DSG, 5-MOP, or their combination significantly reversed the condition and increased the phosphorylated expression of estrogen receptor-α (ERα), sarcoma (Src), Akt/protein kinase B, glycogen synthase kinase-3β (GSK-3β), and the p85 regulatory subunit of phosphatidylinositol 3-kinase p85 (PI3Kp85). At the transcriptional level, expression of the genes mentioned above also increased except for the negative regulation of GSK-3β mRNA. The increased expression of glucose transport-4 (GLUT-4) was meanwhile observed through immunofluorescence. Nevertheless, the synergistic effect of DSG and 5-MOP on improving glycometabolism was not obvious in the present study. These results suggested that DSG and 5-MOP may improve insulin resistance through an ER-mediated PI3K/Akt activation pathway which may be a new strategy for type 2 diabetes mellitus, especially for women in an estrogen-deficient condition.
Highlights
The prevalence of diabetes mellitus is increasing year by year around the world
DSG was obtained from Aoke Biology Research Co., Ltd. (Beijing, China). β-Estradiol was purchased from Aladdin Industrial Corporation (Shanghai, China). 5-MOP, human insulin, dimethyl sulfoxide (DMSO), and wheat germ agglutinin (WGA) dye were purchased from Sigma-Aldrich Co
Double staining with estrogen receptor-α (ERα) and plasma membrane revealed the presence of ERα in plasmalemma, cytoplasm, and nuclei by the use of confocal imaging
Summary
The prevalence of diabetes mellitus is increasing year by year around the world. Does it reduce people’s quality of life, and it leads to death for its series of complications. According to an estimate by the International Diabetes Federation, the global prevalence of diabetes mellitus among adults with 20–79 years of age was 8.3% in 2013 [1]. Menopausal women seemed to have a striking increase in the incidence of type 2 diabetes (T2DM) [2]. We speculated that estrogen may play a vital role in maintaining glucose homeostasis. Despite abundant evidence of the validity of estrogen-containing therapies on alleviating menopausal symptoms [4], many women resorted to herbal medicines to regulate blood glucose because of side effects
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