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R. ANDERSON, Nutrient Requirements and Functions Laboratory, Beltsville Human Nutrition Research Center, USDA, Building 307, Room 224, Beltsville, MD 20705-2350

The causes, control, and prevention of glucose intolerance and type 2 diabetes mellitus are not clear, but there is strong evidence that dietary factors play key roles. The initial steps in increased blood glucose levels usually involve decreased insulin sensitivity and impaired function. To determine possible dietary factors that improve insulin function, aqueous extracts of foods and spices were tested for insulin-potentiating activity in the insulin-dependent utilization of glucose, using a rat epididymal adipocyte assay.

Cinnamon was the most bioactive product, followed by witch hazel, green and black teas, allspice, bay leaves, nutmeg, cloves, mushrooms, and brewer's yeast. The glucose oxidation-enhancing bioactivity was lost from cinnamon, tea, witch hazel, cloves, bay leaf, and allspice by polyvinylpyrrolidone (PVP) treatment, indicating that the active phytochemical(s) are likely to be phenolic in nature. The activity of sage, mushrooms, and brewers's yeast was not removed by PVP.

Since extracts of cinnamon were the most active in increasing insulin activity, we isolated and characterized its most biologically active fractions. We have identified methylhydroxy-chalcone polymers from cinnamon that increase insulin-dependent in vitro glucose metabolism more than 20-fold. The activity of these is relatively specific, since no other cinnamon-derived compounds, fractions, or similar chemicals tested increased the function of insulin similarly.

We have shown that the mechanism of action of these polymers involves the activation of insulin-receptor-kinase and the inhibition of insulin-receptor-phosphatase leading to maximal phosphorylation of the insulin receptor, which is associated with increased insulin sensitivity. We have identified another class of known compounds from tea that also potentiate insulin action more than 20-fold. The most active of these is epigallocatechin gallate.

Our studies suggest that, in addition to their role as antioxidants, specific dietary polyphenol compounds may play a role in enhancing insulin function, and thereby in the prevention and treatment of glucose intolerance and diabetes.