Effekte von flavonoiden/Polyphenolen auf Transporter und Enzyme der Glucose / Glycogen Homöostase in verschiedenen Zelltypen und im Menschen

点击翻译按钮获取中文摘要

The aim of the planned study is to enhance knowledge on the effects of flavonoids/polyphenols on glucose and glycogen homeostasis in transformed and non-transformed cell systems. Hypoglycemic/insulin-like effects reported for certain polyphenols/flavonoids are suggestive for their potential usefulness as antidiabetics. On the other hand, induction of hypoglycemia, especially at high intake of such flavonoids might represent a health risk that also deserves thorough investigation. Information on effects of polyphenols on key enzymes regulating glycogen homeostasis, including glycogen phosphorylase (GP), glycogen synthase (GS) and glycogen synthase kinase (GSK3) are scarce. GSK3 is an important regulator of glycogen synthesis. However, GSK3 is also involved in regulating embryogenesis, cell proliferation and apoptosis e.g. within the context of the Wnt signaling pathway. In the adenomatous polyposis coli (APC) complex as a downstream effector of Wnt, GSK3 is an important constituent.Modulation of GSK3-activity by such food borne compounds may therefore lead to a spectrum of downstream consequences, depending on the cellular/tissue context. Because active GSK-3beta is instrumental for normal APC complex function, ascertaining beta-catenin turnover, its inhibition could lead to detrimental effects e.g. in colon cells. We therefore plan to study effects of flavonoids on key enzymes of glycogen homeostasis (including GSK-3beta) and on cellular glucose transporters, comparing responses in cells of different origin (blood, colon and liver). Comparison of gene expression profiles of key enzymes and regulators of glycogen homeostasis from treated and non-treated cells will help to identify relevant novel biomarkers. Moreover, cellular downstream effects on transcriptional activity, especially by monitoring beta-catenin levels and beta-catenin dependent transcription, will be examined.