2009 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.
Studies conducted this year included evaluating the effect of bay leaves on insulin resistance at collaborating centers. Subjects with type 2 diabetes showed improved glucose utilization and decreased insulin resistance.
This research project has demonstrated that some 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 fats, sugars, and other refined components are also low in chromium and typically low in other potentiators of insulin action. In an in vitro model, cinnamon and bay leaves improved insulin function. In research studies conducted with collaborators at their home institutions, cinnamon and its aqueous extracts improved glucose, insulin, and lipid metabolism of people with varying degrees of impaired insulin function, including glucose intolerance, metabolic syndrome, polycystic ovary syndrome, and type 2 diabetes. Scientists with the Diet, Genomics, and Immunology Laboratory collaborated with scientists at other research centers in studies that found that bay leaves also improved the blood glucose and lipids of people with type 2 diabetes. Chromium status of people could be predicted based upon their degree of insulin sensitivity. Studies with an extract of cinnamon in the hamster, which metabolizes lipids similar to that seen in humans, showed decreased inflammation and improved insulin and lipoprotein signaling pathways with the extract. Using a leukemic cell line, cinnamon controlled the uncontrolled growth of cancer cells. In addition, using a cell culture model of cell swelling, cinnamon polyphenols were effective in controlling cell swelling, which may be of importance in similar swelling associated with brain injury. In summary, the result of this research project demonstrate that components of cinnamon, its polyphenols, bay leaves, and chromium decrease insulin resistance in individuals with type 2 diabetes, and in animal and cell culture models, act to normalize glucose and lipid metabolism, and may also be beneficial in the control of cell swelling associated with brain injury and in the control of unregulated cell growth associated with cancer.
Bay leaves decrease blood glucose, cholesterol, and triglycerides in type 2 diabetic patients. Type 2 diabetes mellitus is a chronic disorder of carbohdyrate metabolism resulting from the decreased function of insulin or resistance to insulin resulting in reduced effectiveness of the usual amount of insulin. Although the causes of type 2 diabetes and cardiovascular diseases are multifactorial, diet definitely plays a role in the incidence and severity of these diseases. The dietary components beneficial in the prevention and treatment of these diseases have not been clearly defined, but it is postulated that spices in the diet contribute to prevention. We have shown previously that aqueous extracts of spices such as cinnamon, cloves, bay leaves, and turmeric display insulin-enhancing activity in cell culture (in vitro) and in animal studies. In a human study conducted in Pakistan bay leaves improved sugar and fat metabolism in people with type 2 diabetes. Forty people with type 2 diabetes were divided into 4 groups and given capsules containing 1, 2, or 3 g of ground bay leaves per day for 30 days or a placebo followed by a 10 day washout period. All three levels of bay leaves led to significant improvements in blood sugar, total cholesterol, LDL and HDL cholesterol, and triglycerides. These data are important to scientists, medical personnel, and the millions of people world-wide showing early signs of diabetes and elevated blood lipids.
Khan, A., Kaman, G., Anderson, R.A. 2008. Bay Leaves Improve Glucose and Lipid Profile of People with Type 2 Diabetes. Plant Foods for Human Nutrition.
Qin, B., Dawson, H.D., Polansky, M.M., Anderson, R.A. 2009. Cinnamon extract attenuates TNF-alpha-induced Intestinal lipoprotein ApoB48 overproduction by regulating inflammatory, insulin and lipoprotein pathways in enterocytes. Hormone and Metabolic Research. 41:1-7.
Roussel, A., Hininger, I., Waters, R., Osman, M., Fernholz, K., Anderson, R.A. 2009. EDTA chelation therapy, without added vitamin C, decreases oxidative DNA damage and lipid peroxidation. Alternative Medicine Review. 14:56-61.