title: Fructose, but not glucose, impairs insulin signaling in the three major insulin-sensitive tissues.
abstract: Human studies support the relationship between high intake of fructose-sweetened beverages and type 2 diabetes, but there is a debate on whether this effect is fructose-specific or it is merely associated to an excessive caloric intake. Here we investigate the effects of 2 months' supplementation to female rats of equicaloric 10% w/v fructose or glucose solutions on insulin sensitivity in target tissues. Fructose supplementation caused hepatic deposition of triglycerides and changed the fatty acid profile of this fraction, with an increase in monounsaturated and a decrease in polyunsaturated species, but did not cause inflammation and oxidative stress. Fructose but not glucose-supplemented rats displayed an abnormal glucose tolerance test, and did not show increased phosphorylation of V-akt murine thymoma viral oncogene homolog-2 (Akt) in white adipose tissue and liver after insulin administration. In skeletal muscle, phosphorylation of Akt and of Akt substrate of 160 kDA (AS160) was not impaired but the expression of the glucose transporter type 4 (GLUT4) in the plasma membrane was reduced only in fructose-fed rats. In conclusion, fructose but not glucose supplementation causes fatty liver without inflammation and oxidative stress and impairs insulin signaling in the three major insulin-responsive tissues independently from the increase in energy intake.
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Spain.|Institute of Biomedicine, University of Barcelona, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Baena
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Spain.|Institute of Biomedicine, University of Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Sangüesa
authors.affiliation: IMDEA Food. CEI UAM+CSIC, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Dávalos
authors.affiliation: IMDEA Food. CEI UAM+CSIC, Madrid, Spain.
authors.forename: María-Jesús
authors.initials: MJ
authors.lastname: Latasa
authors.affiliation: CIBER Fisiología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Spain.|Lipid Clinic, Endocrinology and Nutrition Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Aleix
authors.initials: A
authors.lastname: Sala-Vila
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Spain.|Institute of Biomedicine, University of Barcelona, Spain.|CIBER Fisiología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Spain.
authors.forename: Rosa María
authors.initials: RM
authors.lastname: Sánchez
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Spain.|Institute of Biomedicine, University of Barcelona, Spain.|CIBER Fisiología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Roglans
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Spain.|Institute of Biomedicine, University of Barcelona, Spain.|CIBER Fisiología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Laguna
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Spain.|Institute of Biomedicine, University of Barcelona, Spain.|CIBER Fisiología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Alegret
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D004032:Diet / Q000379:methods; D005234:Fatty Liver / Q000139:chemically induced* / Q000473:pathology; D005632:Fructose / Q000008:administration & dosage*; D005947:Glucose / Q000008:administration & dosage*; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D008099:Liver / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology; D051381:Rats; D015398:Signal Transduction; D013549:Sweetening Agents / Q000378:metabolism*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D013549:Sweetening Agents; D005632:Fructose; D005947:Glucose