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Investigations into the effects of a flavonoid- rich berry extract on glucose transport in intestinal epithelial cells and muscle

Student thesis: Doctoral ThesisDoctor of Philosophy

Flavonoids are a broad collection of polyphenolic compounds ubiquitously found in foods of plant origin. Previous studies suggested that they are beneficial in protecting against many chronic diseases, such as cancers, cardiovascular diseases and neurological disorders. There is also evidence that flavonoids have beneficial effects on modifying glucose absorption and are thus regarded as potential anti-diabetic agents. To address this we investigated the effects of a flavonoid-rich berry extract on glucose transport in intestinal epithelial Caco-2 cells and C2C12 muscle cells. In Caco-2 cells, acute exposure to berry extract inhibited glucose uptake. Prolonged incubation down-regulated the gene expression of SLUT2 and SGLT1, with a concomitant up-regulation of let-7a miRNA. Using bioinformatic tools, let-7a is predicted to target the mRNA of GLUT2, potentially down-regulating its expression. In C2C12 myotubes, chronic incubation of berry extract did not have any effect on basal or insulin-stimulated glucose uptake.
Taken together, these data suggested that the acute inhibitory effects of berry flavonoids on glucose transport are specific to intestinal glucose transporters. These compounds may be useful for regulating the rate of glucose absorption from the diet; however, they are less effective modifiers of peripheral glucose transport.
 Studies were also carried out on the molecular basis of alcoholic myopathy, using the C2C12 muscle cell model. This provides not only an opportunity to study the pathogenic basis of a common disorder but also to compare putative pathways that may be modulated my myotoxins and myoprotectants. The results of microarray studies showed that alcohol altered the expression of genes related to multiple cellular functions, including insulin signalling, muscle contraction and protein synthesis. On the other hand, microarray studies demonstrated that berry extract was a potent inducer of cellular antioxidant defence system. This indicated that berry extract might act as a dietary strategy to protect cells against ethanol-induced oxidative damage.

Original languageEnglish
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Award date2014

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