Apple polyphenol extract improves insulin sensitivity in vitro and in vivo in animal models of insulin resistance
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AutorManzano, Manuel; Girón González, María Dolores; Vílchez Rienda, José Dámaso; Sevillano Tripero, Natalia; El-Azem de Haro, Nuri; Rueda Cabrera, Ricardo; Salto González, Rafael; López-Pedrosa, José M.
Apple polyphenol extractInsulin sensitivityBlood glucose uptakeSkeletal muscleDiabetes
Manzano, M.; et al. Apple polyphenol extract improves insulin sensitivity in vitro and in vivo in animal models of insulin resistance. Nutrition and Metabolism, 13: 32 (2016). [http://hdl.handle.net/10481/44824]
PatrocinadorThis research was supported by funds from Abbott Laboratories S.A.
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 (PPARγ) 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.