Type 2 diabetes mellitus is predominantly a disease of Western societies. Although a number of factors may be working in synergy to account for the difference in prevalence between Eastern and Western cultures, the role of dietary composition cannot be overlooked. In Western populations, the daily consumption of phyto estrogens of the isoflavone class is less than 1 mg per day, compared to 50-100 mg per day in average Asian diets. At physiologically relevant concentrations, isoflavones have been shown to enhance beta cell insulin secretion, and to increase their sensitivity to glucose in vitro. In addition, an isoflavone-rich diet increases liver and adipocyte mRNA insulin receptor expression. Thus, isoflavones may enhance beta cell insulin secretion and peripheral tissue insulin responsivness in vivo; the two major defects associated with type 2 diabetes.
The specific aims of this proposal are to: 1) Systematically evaluate the concentration-dependent effect of three dietary isoflavones- genistein, didzein and glycitein- on beta cell function in vitro. Response will be measured by insulin gene expression, intracellular insulin accumulation and insulin levels in the medium; 2) Determine insulin dependent responsivness of human adipocytes in the presence of these three isoflavones. This will be quantitated by glycogen synthase activity and glucose uptake 3) Quantitate the effect of dietary isoflavones on parameters of glycemic control when given in the acute setting to subjects with Type 2 diabetes. Specific endpoints include glycemic control, insulin levels, lipid profiles and free fatty acid levels; and 4) Quantitate the effect of isoflavones when given in the chronic setting to subjects with Type 2 diabetes. In addition to the serum measurements outlined above, the chronic study will utilize glucose clamp techniques and intravenous glucose tolerance tests to further assess glucose utilization and insulin secretion.
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