Background: Apple polyphenols could represent a novel nutritional approach in the management and control of blood glucose, especially in type 2 diabetics. The aim of this study was to test the therapeutic potential of an apple polyphenol extract (APE) in an insulin-resistant rat model and to determine the molecular basis of insulin sensitivity action in skeletal muscle cells. Methods: Acute effect of APE on the postprandial hyperglycemic response was assayed in 15 week old obese Zucker rats (OZR), by using a meal tolerance test (MTT). The ability of APE to improve whole peripheral insulin sensitivity was also assayed in a chronic study by using the euglycemic-hyperinsulinemic clamp technique. To elucidate the molecular mechanisms, rat L6 myotubes were used. Glucose uptake was measured by using 2-[3H]- Deoxy-Glucose (2-DG) and specific inhibitors, as well as phosphorylation status of key kinases, were used to determine the implicated signaling pathway. Results: In vivo study showed that nutritional intervention with APE induced an increase of insulin sensitivity with an increase of glucose infusion rate (GIR) of 45 %. Additionally, in vitro results showed a synergistic effect between APE and insulin as well as increased glucose uptake through GLUT4 translocation in muscle cells. This translocation was mediated by phosphatydil inositol 3-kinase (PI3K) and peroxisome proliferator-activated receptor-gamma (PPAR) signaling pathways. Conclusions: As a whole, this study describes the mechanisms involved in the insulin sensitizing effect of APE, which could be considered a promising ingredient for inclusion in nutritional products focused on the management of chronic diseases such as diabetes.
CITATION STYLE
Manzano, M., Giron, M. D., Vilchez, J. D., Sevillano, N., El-Azem, N., Rueda, R., … Lopez-Pedrosa, J. M. (2016). Apple polyphenol extract improves insulin sensitivity in vitro and in vivo in animal models of insulin resistance. Nutrition and Metabolism, 13(1). https://doi.org/10.1186/s12986-016-0088-8
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