Obesity induced type 2 diabetes is common in the US and we seek to prevent the onset of the disease by reducing lipotoxicity as well as mitigating oxidative stress in those already suffering from it through the introduction of an innovative new dietary supplement. Elevated concentration of free fatty acids in plasma in obese subjects exerts lipotoxicity on skeletal muscles, pancreatic beta cells and cardiomyocytes, leading to insulin resistance, insulin deficiency and diabetic cardiomyopathy, respectively. Increased oxidative stress and reduced antioxidant defenses are detected in diabetic patients. In the preliminary studies, the extract from bamboo Phyllostachys edulis was found to efficiently protect a variety of mamamlian cells from lipotoxicty. It also posesses high levels of antioxidant capacity and stimulates O2 consumption in cells indicating a potential to increase celluar oxidative capacity. This proposal explores the mechanisms and the application of lipo-detoxification and antioxidantive effects of the bamboo extract (BM). The specific aims are: 1. To investigate the mechanisms of BM in preventing lipotoxicity in cells in culture. We hypothesize that the high antioxidant capacity and O2 consumption-enhancing effects of BM contribute to lipo-detoxification. The influences of BM on cultured muscle cells under lipotoxic conditions are investigated, with emphasis on relieving oxidative stress and regulating the expression level of genes related to oxidative capacity. The functional component(s) in BM will be fractionated and possible synergistic effects are tested. 2. To investigate the systemic effects of BM as a dietary supplement to Zucker Diabetic Fatty (ZDF) rats. We hypothesize that the symptoms of diabetes and diabetic complication are ameliorated in ZDF rats by BM supplemetation. Glucose and insulin levels in blood, antioxidant level and oxidative stress markers in blood and muslces, cell death in beta cells and cardiomyocytes, oxidative capacity and fatty acid oxidation - related gene expression in skeletal and cardiac muscles will be examined. Zucker Lean Rats are used as a control. Knowledge obtained from this study supports the long term goal of the principal investigator to develop the BM into a diabetes/ diabetic complication preventing food supplement. It will serve as a cost-effective alternative to conventional therapeutics utilized in post-diagnosis treatment for diabetes that will improve the quality of life for large numbers of afflicted individuals in the US and ultimately throughout the world.

R21AT003874

2006-09-30

2009-08-31