Browsing by Author "Zhen, W."

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    Baicalein Protects against Type 2 Diabetes via Promoting Islet β-Cell Function in Obese Diabetic Mice
    Fu, Y.; Luo, J.; Jia, Z.; Zhen, W.; Zhou, K.; Gilbert, Elizabeth R.; Liu, D.; Lee, H. (Hindawi, 2014)
    In both type 1 (T1D) and type 2 diabetes (T2D), the deterioration of glycemic control over time is primarily caused by an inadequate mass and progressive dysfunction of β-cell, leading to the impaired insulin secretion. Here, we show that dietary supplementation of baicalein, a flavone isolated from the roots of Chinese herb Scutellaria baicalensis, improved glucose tolerance and enhanced glucose-stimulated insulin secretion (GSIS) in high-fat diet (HFD-) induced middle-aged obese mice. Baicalein had no effect on food intake, body weight gain, circulating lipid profile, and insulin sensitivity in obese mice. Using another mouse model of type 2 diabetes generated by high-fat diet (HFD) feeding and low doses of streptozotocin injection, we found that baicalein treatment significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in these middle-aged obese diabetic mice, which are associated with the improved islet β-cell survival and mass. In the in vitro studies, baicalein significantly augmented GSIS and promoted viability of insulin-secreting cells and human islets cultured either in the basal medium or under chronic hyperlipidemic condition. These results demonstrate that baicalein may be a naturally occurring antidiabetic agent by directly modulating pancreatic β-cell function.
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    Dehydroepiandrosterone protects vascular endothelial cells against apoptosis through a G alpha(i) protein-dependent activation of phosphatidylinositol 3-kinase/Akt and regulation of antiapoptotic Bcl-2 expression
    Liu, D. M.; Si, H. W.; Reynolds, K. A.; Zhen, W.; Jia, Z. Q.; Dillon, J. S. (Endocrine Society, 2007-07)
    The adrenal steroid dehydroepiandrosterone (DHEA) may improve vascular function, but the mechanism is unclear. In the present study, we show that DHEA significantly increased cell viability, reduced caspase-3 activity, and protected both bovine and human vascular endothelial cells against serum deprivation-induced apoptosis. This effect was dose dependent and maximal at physiological concentrations (0.1-10 nM). DHEA stimulation of bovine aortic endothelial cells resulted in rapid and dose-dependent phosphorylation of Akt, which was blocked by LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), the upstream kinase of Akt. Accordingly, inhibition of PI3K or transfection of the cells with dominant-negative Akt ablated the antiapoptotic effect of DHEA. The induced Akt phosphorylation and subsequent cytoprotective effect of DHEA were dependent on activation of G alpha(i) proteins, but were estrogen receptor independent, because these effects were blocked by pertussis toxin but not by the estrogen receptor inhibitor ICI182,780 or the aromatase inhibitor aminoglutethimide. Finally, DHEA enhanced antiapoptotic Bcl-2 protein expression, its promoter activity, and gene transcription attributable to the activation of the PI3K/Akt pathway. Neutralization of Bcl-2 by antibody transfection significantly decreased the antiapoptotic effect of DHEA. These findings provide the first evidence that DHEA acts as a survival factor for endothelial cells by triggering the G alpha(i)-PI3K/Akt-Bcl-2 pathway to protect cells against apoptosis. This may represent an important mechanism underlying the vascular protective effect of DHEA.