The effects and mechanisms of saponins of panax notoginseng on glucose and lipid metabolism in 3T3-L1 cells

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NO FULL TEXT AVAILABLE. Access is restricted indefinitely. ----- Type 2 diabetes is a metabolic disorder which has been posed as a serious health problem in our present society. In light of the escalating prevalence of the disease and widespread evidence of progression to cardiovascular complications, there is a need to discover new agents to successfully treat this multifacet disorder. Resistance to insulin-mediated glucose uptake and deregulation of lipid metabolism are early and major hallmarks in the development of type 2 diabetes. The aim of this thesis was to determine the effects and mechanisms of saponins of Panax notoginseng (SPN) on glucose and lipid metabolism. 3T3-L1 adipocytes was utilized to study whether this naturally occurring agent, which has been used in the treatment of ischemic cardio- cerebral vascular disease throughout China for years, improves insulin-mediated glucose uptake and lowers lipid levels in vivo. 3T3-L1 adipocytes were cultured and treated with 100 nM insulin alone or with concentrations of 10, 50, 100 and 200 pg/ml SPN, respectively. [3H]2-deoxyglucose glucose uptake, GLUT4 immunofluorescence imaging and glycogen synthesis assay were carried out to determine the effects of SPN on glucose metabolism. In addition, lipid staining and lipolysis assay were carried to study the effects of SPN on lipid metabolism. The results in Chapter 2 indicate that SPN consist of properties that improve glucose metabolism in 3T3-L1 cells. SPN significantly increased insulin-mediated glucose uptake in a dose-dependent manner. Immunofluorescence imaging and analysis showed that SPN increased GLUT4 in the plasma membrane. Furthermore, glycogen synthesis augmented, whereby the incorporation of D-[U-I4C] glucose into glycogen was enhanced with SPN treatment in 3T3-L1 cells. These findings suggest that SPN may have a direct effect upon lowering glucose levels in type 2 diabetes. Furthermore, results in Chapter 3 of this thesis illustrates that SPN also exert effects that regulate lipid metabolism. Lipid staining showed SPN significantly decreased lipid content 3T3-L1 adipocytes. In addition, SPN significantly inhibited lipolysis in vitro, indicating that this naturally occurring agent may decrease free fatty acid delivery to the liver thereby subsequently reducing hepatic glucose production. In effort to discover a new anti-diabetic agent that achieves both treatment of type 2 diabetes and prevention of diabetic complications, this study supports that SPN is a potential agent that is capable of directly lowering blood glucose and lipid levels in type 2 diabetic patients. Further research with both in animal models and clinical trials, as described in Chapter 4, is needed to establish that SPN has high potential to be used as an agent for diabetes and its vascular complications. These findings may prove to be highly valuable to our society.
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