Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/53946
Title: Liquid fructose down-regulates liver insulin receptor substrate 2 and gluconeogeneic enzymes by modifying nutrient sensing factors in rats
Author: Rebollo de Grado, Alba
Roglans i Ribas, Núria
Baena Muñoz, Miguel
Padrosa, Anna
Sánchez Peñarroya, Rosa M.
Merlos Roca, Manuel
Alegret i Jordà, Marta
Laguna Egea, Juan Carlos
Keywords: Resistència a la insulina
Fetge
Fructosa
Insulin resistance
Liver
Fructose
Issue Date: Feb-2014
Publisher: Elsevier B.V.
Abstract: High consumption of fructose-sweetened beverages has been linked to a high prevalence of chronic metabolic diseases. We have previously shown that a short course of fructose supplementation as a liquid solution induces glucose intolerance in female rats. In the present work, we characterized the fructose-driven changes in the liver and the molecular pathways involved. To this end, female rats were supplemented or not with liquid fructose (10%, w/v) for 7 or 14 days. Glucose and pyruvate tolerance tests were performed, and the expression of genes related to insulin signaling, gluconeogenesis and nutrient sensing pathways was evaluated. Fructose-supplemented rats showed increased plasma glucose excursions in glucose and pyruvate tolerance tests and reduced hepatic expression of several genes related to insulin signaling, including insulin receptor substrate 2 (IRS-2). However, the expression of key gluconeogenic enzymes, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, was reduced. These effects were caused by an inactivation of hepatic forkhead box O1 (FoxO1) due to an increase in its acetylation state driven by a reduced expression and activity of sirtuin 1 (SIRT1). Further contributing to FoxO1 inactivation, fructose consumption elevated liver expression of the spliced form of X-box-binding-protein-1 as a consequence of an increase in the activity of the mammalian target of rapamycin 1 and protein 38-mitogen activated protein kinase (p38-MAPK). Liquid fructose affects both insulin signaling (IRS-2 and FoxO1) and nutrient sensing pathways (p38-MAPK, mTOR and SIRT1), thus disrupting hepatic insulin signaling without increasing the expression of key gluconeogenic enzymes.
Note: Versió postprint del document publicat a: http://dx.doi.org/10.1016/j.jnutbio.2013.10.014
It is part of: Journal of Nutritional Biochemistry, 2014, vol. 25, num. 2, p. 250-258
Related resource: http://dx.doi.org/10.1016/j.jnutbio.2013.10.014
URI: http://hdl.handle.net/2445/53946
ISSN: 0955-2863
Appears in Collections:Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)

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