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Title: The chronic and acute effects of (poly)phenols on sucrase isomaltase using the Caco-2/TC7 cell model
Author: Pyner, Alison Heather
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2007
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Evidence from animal models and human intervention studies indicates that polyphenols can potentially attenuate the postprandial glycaemic response by inhibition of α-glucosidases, critical for carbohydrate digestion, and by attenuation of monosaccharide transport across small intestinal enterocytes. Therefore, this study evaluated the effect of polyphenols, including an oleuropein-rich olive leaf extract, on sucrose hydrolysis and transport. Controlling the glycaemic response reduces the risk of development and progression of type 2 diabetes, much like the anti-diabetic drug acarbose. An in vitro inhibition assay for sucrase and maltase activity was optimised using Caco-2/TC7 cells as a human enzyme source and compared to a rat enzyme. Inhibitors were more effective on human compared to rat sucrase while the reverse was true for maltase. Chronic sucrose exposure led to altered N- and O-glycosylation and the sucrase Km increased by 15% compared to cells cultured in glucose. A chronic 3-day treatment with 1.5 mg/mL olive leaf extract reduced the sucrase specific activity by 31% and 26% for cells cultured in glucose and sucrose, respectively. Sucrase N-glycosylation increased in cells cultured in sucrose and this could have led to the decrease in Km. Oleuropein treatment decreased cell surface sucrase by 41% when cultured long-term in glucose but not sucrose. Transport studies for glucose-cultured cells showed that chronic treatment reduced sucrase hydrolysis and attenuated of fructose transport and GLUT2-mediated glucose transport. These results show for the first time that chronic treatment with olive polyphenols can reduce the sucrose hydrolysis and modulate glucose and fructose transport. Changes in post-translational modifications of sucrase with different treatments opens up new areas of research. Investigations are warranted regarding the use of olive leaf extract in humans for glycaemic control after sugar consumption with the suggestion that sugar intake might impact the effectiveness of the treatment.
Supervisor: Williamson, Gary ; McKeown, Lynn Sponsor: ERC
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available