|Roussel, Anne Marie - J.FOURIER U, NVMC, FR|
Submitted to: Bioactive Natural Products
Publication Type: Book / Chapter
Publication Acceptance Date: November 24, 2008
Publication Date: January 4, 2010
Citation: Cao, H., Roussel, A., Anderson, R.A. 2010. Green tea: molecular targets in glucose uptake, inflammation, and insulin signaling pathways. Comprehensive Bioactive Natural Products. Vol. 2-Efficiacy, Safety & Clinical Evaluation I, Stadium Press LLC, P. 429-448. Technical Abstract: Obesity is a major public health problem that leads to increased risk of developing diabetes, cardiovascular, and related diseases. The number of overweight and obese Americans has increased since the 1960s, and obesity may be responsible for as many as 300,000 deaths and medical costs in excess of $100 billion annually in the U.S. alone. Drugs to reduce obesity and related disorders have been largely ineffective resulting in the evaluation of complementary and alternative approaches to prevent development of these chronic diseases and conditions. A number of bioactive plant components have been tested, including cinnamon, used to alleviate the signs and symptoms of insulin resistance and type 2 diabetes due to its insulin-like activity. This study tested the hypothesis that a cinnamon polyphenol extract (CPE) induces molecular changes that contribute to its insulin-like and anti-inflammatory properties. Real-time PCR was used to compare the effects of CPE and insulin on the expression of 43 genes encoding the glucose transporter (GLUT) family, insulin signaling components, the anti-inflammatory tristetraprolin (TTP) family, and pro-inflammatory cytokines in cultured mouse adipocytes and RAW cell line macrophages. The major findings are: 1) CPE, but not insulin, significantly increased GLUT1 mRNA levels up to 7- and 3-fold in adipocytes and macrophages, respectively; 2) CPE increased TTP mRNA levels up to 10- and 2-fold over 2-16 h in adipocytes and macrophages, respectively; 3) insulin stimulated TTP gene expression, but its effect returned to baseline levels within 2 h; 4) vascular endothelial growth factor A (VEGFA) mRNA levels were decreased 50% in both cell systems treated with CPE or insulin; and 5) CPE and insulin decreased the expression of most genes encoding insulin-signaling pathway proteins. The insulin-like effects of CPE include rapid induction of TTP and reduction of VEGFA and insulin-signaling pathway gene expression. CPE, unlike insulin, induces sustained GLUT1 and TTP expression. This is important because GLUT1 is a major glucose transporter, and the absence of TTP protein exacerbates arthritis and autoimmune diseases, and its expression is reduced in adipose tissue of obese people with metabolic syndrome and also in the brains of suicide victims. This study also shows that CPE regulates the expression VEGFA, which is an angiogenic cytokine responsible for new blood vessel formation in adipose tissue and solid tumor.