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 |
URI: | http://hdl.handle.net/2445/53946 |
Related resource: | http://dx.doi.org/10.1016/j.jnutbio.2013.10.014 |
ISSN: | 0955-2863 |
Appears in Collections: | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
637133.pdf | 426.99 kB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.