|Graves, C -|
Submitted to: Phytomedicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 31, 2009
Publication Date: November 1, 2010
Citation: Cao, H., Graves, C.J., Anderson, R.A. 2010. Cinnamon extract regulates glucose transporter and insulin-signaling gene expression in mouse adipocytes. Phytomedicine. 17(3):1027-1032. Interpretive Summary: Bioactive components in plant products have been used for the prevention and treatment of various diseases since ancient history. One of the major classes of bioactive compounds is plant polyphenols, which are found in seeds, fruits, leaves, and bark. These compounds are widely present in the diet and are potentially important to human health. Cinnamon and other spices have insulin-like activity in vitro, and are proposed to be effective in the prevention and treatment of obesity and diabetes. Multiple studies provide evidence for supporting the proposal that cinnamon polyphenol extract (CPE) has insulin-like activity in cells, animals, and people with type 2 diabetes. However, some studies have not reported positive effects of cinnamon in diabetic patients. Recent studies suggest that CPE may have other potential health benefits, and that it demonstrates multiple effects in animal and human studies. We tested the hypothesis that CPE has insulin-like and additional effects on the regulation of genes in fat cells taken from mice. We investigated the effects of CPE on the function of 43 genes involved with sugar metabolism and immune function in mouse fat cells. Our results indicate that CPE is capable of regulating the function of multiple genes in fat cells and suggest that the health benefits of cinnamon are due to both its insulin-like action and these additional effects.
Technical Abstract: Cinnamon has been used to treat people with type 2 diabetes based on the insulin-like activity of cinnamon polyphenol extract (CPE) observed in cell culture, animal, and human studies. Molecular characterization of the effect of CPE, however, is limited. This study tested the hypothesis that CPE has insulin-like and insulin-independent effects on mouse 3T3-L1 adipocytes at the molecular level. Quantitative real-time PCR was used to investigate CPE effects on the expression of 43 genes coding for the glucose transporter (GLUT) family, insulin-signaling components, adipokines, the anti-inflammatory tristetraprolin (TTP/zinc finger protein 36) family, pro-inflammatory cytokines, and related gene targets in mouse 3T3-L1 adipocytes. CPE (100 mg/L) increased GLUT1 mRNA levels by 2-7 fold greater than control-treated adipocytes after 2-16 h. CPE increased TTP mRNA levels by up to 10- and 2-fold that of the control after 0.5-1.5 and 4-16 h, respectively, but it decreased TTP homologue mRNA levels after 16 h. The levels of vascular endothelial growth factor (VEGF) mRNA, a putative target of TTP, were decreased 40-50% by CPE treatment for 0.5-4 h. CPE decreased the expression of most genes encoding insulin signaling pathway proteins. The presence of CPE resulted in insulin-like effects including rapid induction of TTP mRNA, and the reduction of mRNA for VEGF and genes in the insulin-signaling pathway. CPE also induced insulin-independent effects, including sustained increases in GLUT1 and TTP expression. These results indicate that CPE regulates multiple gene expression targets in adipocytes and suggests that the health benefits of cinnamon are due to both its insulin-like and insulin-independent effects.