2008 Annual Report
1a.Objectives (from AD-416)
Overall objective of the proposed research is to help control the incidence of impaired glucose metabolism and decrease the conversion of glucose intolerance to diabetes. Specific objectives include the following. 1)Elucidate the role of Cr in the onset of impaired glucose metabolism using a stress-induced rat model for Cr deficiency. 2)Determine methods to assess Cr status and elucidate its functions in human nutrition. 3)Define the role and mechanistic effects of insulin potentiating polyphenols from cinnamon on intracellular signals that regulate insulin-induced glucose uptake and oxidative stress.
1b.Approach (from AD-416)
Compounds that enhance insulin activity lead to a more sensitive response to insulin and improve glucose tolerance. Increased levels of stress lead to loss of nutrients including chromium (Cr), a nutrient that is involved in glucose and insulin metabolism. We propose to elucidate the role of Cr in a stress-induced diabetes rat model. Steroid-induced diabetes in people taking steroids such as prednisone has been shown to be reversed by increased intake of chromium. This project is designed to elucidate the role of the chronic stress of low level administration of the steroid, dexamethasone, in the augmentation of deficiency of chromium. These studies will facilitate our collaborative human study to elucidate the roles of Cr in human nutrition and also methods to assess Cr status. There are currently no reliable methods to assess Cr status. This study will combine reliable analytical measures of chromium status with studies to elucidate the function of chromium in human nutrition. We also propose to define the role and mechanistic effects of insulin potentiating polyphenols from cinnamon on intracellular signals that regulate insulin-induced glucose uptake, oxidative stress and NF-'B activation. These studies should lead to a greater understanding of the roles of chromium and polyphenols from cinnamon in the prevention and alleviation of glucose intolerance and type 2 diabetes.
Research in this laboratory has demonstrated that the risk factors associated with type-2 diabetes and cardiovascular diseases may be alleviated by compounds that improve insulin function, including chromium and other insulin-potentiating factors found in foods, herbs, and spices. Modern diets that are high in fat, sugars, and other refined components may also be low in chromium and other substances that enhance insulin action. In a clinical study conducted in collaboration with scientists at the Pennington Biomedical Research Center, giving supplemental chromium as chromium picolinate to subjects who had type 2 diabetes led to improved insulin function and overall health. Subjects responding optimally to supplemental chromium could be predicted by their insulin sensitivity based on the response observed during glucose clamp studies. Insulin sensitivity is usually predicted based on glucose and insulin values observed during an oral glucose tolerance test, and should predict those who will respond to supplemental chromium. Polyphenols found in cinnamon also improve insulin function as well as decreasing the degree of inflammation present. Inflammation is not only associated with common diseases such as arthritis and allergies but has also been linked to obesity. In cell culture, cinnamon polyphenols increased the anti-inflammatory protein tristetraprolin that leads to decreases in several proteins associated with inflammation and obesity. The protective effects of polyphenols isolated from green tea and cinnamon were also investigated in brain cells in culture subjected to oxygen-glucose deprivation as an in vitro model of restricted blood flow or ischemic injury (similar to that seen in strokes). Polyphenol extracts from green tea and cinnamon blocked the negative effects of oxygen-glucose deprivation in these cells. However, individual polyphenol components of either green tea or cinnamon did not protect. Likewise, resveratrol, a polyphenolic antioxidant found in grapes and blueberries, did not prevent swelling. One possible mechanism by which these tea and cinnamon polyphenols attenuate brain cell swelling in ischemic injury may be through preventing mitochondrial dysfunction. Conducted as part of the National Program for Human Nutrition 107 Action Plan Component 5, Health Promoting Properties of Plant and Component 6, Relationship between Diet, Genetics, Lifestyle, and the Prevention of Obesity and Disease.
Cinnamon polyphenols regulate gene expression of pro- and anti-inflammatory genes. Past studies in this laboratory have shown that cinnamon is beneficial in the control of risk factors associated with diabetes and cardiovascular diseases. The purpose of studies reported this year was to determine the effects of a water-soluble cinnamon extract (CE) on immune function. Beneficial effects of CE on regulatory proteins that control inflammation was evaluated. The CE was shown to increase the anti-inflammatory protein tristetraprolin which leads to decreases in three important pro-inflammatory factors, including granulocyte-macrophage colony-stimulating factor/colony-stimulating factor 2, tumor necrosis factor-alpha, and vascular endothelial growth factor. Since inflammation is a key adverse component of many chronic diseases including obesity, diabetes, and cardiovascular diseases, these studies demonstrate the potential beneficial effects of cinnamon in the prevention and/or alleviation of these chronic diseases, which would lead to decreased morbidity, mortality, and health care costs. These studies were conducted under the National Program for Human Nutrition-107, Component 4, Nutrient Requirements and Component 5, Health Promoting Properties of Plant and Animal Foods.
5.Significant Activities that Support Special Target Populations
|Number of Active CRADAs||2|
|Number of Non-Peer Reviewed Presentations and Proceedings||4|
|Number of Newspaper Articles and Other Presentations for Non-Science Audiences||1|
Cao, H., Lin, R., Ghosh, S., Anderson, R.A., Urban Jr, J.F. 2008. Production and characterization of ZFP36L1 antiserum against recombinant protein from Escherichia coli. Biotechnology Progress. 24(2)326-333.
Cao, H., Urban Jr, J.F., Anderson, R.A. 2008. Insulin increases tristetraprolin and decreases VEGF gene expression in mouse 3T3-L1 adipocytes. Obesity. 16:1208-1218.
Qin, B., Anderson, R.A., Adeli, K. 2008. Tumor necrosis factor-alpha directly stimulates the overproduction of hepatic apolipoprotein B100-containing VLDL via impairment of hepatic insulin signaling. American Journal of Physiology - Gastrointestinal and Liver Physiology. 294:G1120-29.
Wang, Z.Q., Qin, J., Martin, J., Zhang, X.H., Sereda, O., Anderson, R.A., Pinsonat, P., Cefalu, W.T. 2007. Phenotype of subjects with type 2 diabetes mellitus may determine clinical response to chromium suppplementation. Metabolism. 56:1652-5.
Cao, H., Urban Jr, J.F., Anderson, R.A. 2008. Cinnamon polyphenol extract affects immune responses by regulating anti- and proinflammatory and glucose transporter gene expression in mouse macrophages. Journal of Nutrition. 138(5):833-840.