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Fernando Escrivá Departamento de Bioquímica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
Centro de Biología Molecular ‘Severo Ochoa’, Facultad de Ciencias, Universidad Autónoma, Campus de Cantoblanco, 28049 Madrid, Spain
Area de Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla La Mancha, 13071 Ciudad Real, Spain
Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, 28922 Alcorcón, Madrid, Spain

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M Lucía Gavete Departamento de Bioquímica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
Centro de Biología Molecular ‘Severo Ochoa’, Facultad de Ciencias, Universidad Autónoma, Campus de Cantoblanco, 28049 Madrid, Spain
Area de Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla La Mancha, 13071 Ciudad Real, Spain
Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, 28922 Alcorcón, Madrid, Spain

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Yasmín Fermín Departamento de Bioquímica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
Centro de Biología Molecular ‘Severo Ochoa’, Facultad de Ciencias, Universidad Autónoma, Campus de Cantoblanco, 28049 Madrid, Spain
Area de Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla La Mancha, 13071 Ciudad Real, Spain
Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, 28922 Alcorcón, Madrid, Spain

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Coralia Pérez Departamento de Bioquímica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
Centro de Biología Molecular ‘Severo Ochoa’, Facultad de Ciencias, Universidad Autónoma, Campus de Cantoblanco, 28049 Madrid, Spain
Area de Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla La Mancha, 13071 Ciudad Real, Spain
Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, 28922 Alcorcón, Madrid, Spain

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Nilda Gallardo Departamento de Bioquímica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
Centro de Biología Molecular ‘Severo Ochoa’, Facultad de Ciencias, Universidad Autónoma, Campus de Cantoblanco, 28049 Madrid, Spain
Area de Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla La Mancha, 13071 Ciudad Real, Spain
Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, 28922 Alcorcón, Madrid, Spain

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Carmen Alvarez Departamento de Bioquímica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
Centro de Biología Molecular ‘Severo Ochoa’, Facultad de Ciencias, Universidad Autónoma, Campus de Cantoblanco, 28049 Madrid, Spain
Area de Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla La Mancha, 13071 Ciudad Real, Spain
Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, 28922 Alcorcón, Madrid, Spain

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Antonio Andrés Departamento de Bioquímica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
Centro de Biología Molecular ‘Severo Ochoa’, Facultad de Ciencias, Universidad Autónoma, Campus de Cantoblanco, 28049 Madrid, Spain
Area de Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla La Mancha, 13071 Ciudad Real, Spain
Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, 28922 Alcorcón, Madrid, Spain

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Manuel Ros Departamento de Bioquímica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
Centro de Biología Molecular ‘Severo Ochoa’, Facultad de Ciencias, Universidad Autónoma, Campus de Cantoblanco, 28049 Madrid, Spain
Area de Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla La Mancha, 13071 Ciudad Real, Spain
Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, 28922 Alcorcón, Madrid, Spain

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José M Carrascosa Departamento de Bioquímica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
Centro de Biología Molecular ‘Severo Ochoa’, Facultad de Ciencias, Universidad Autónoma, Campus de Cantoblanco, 28049 Madrid, Spain
Area de Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla La Mancha, 13071 Ciudad Real, Spain
Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, 28922 Alcorcón, Madrid, Spain

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Insulin resistance develops with ageing in humans and rodents. Here, we have studied the evolution of insulin sensitivity with ageing trying to discriminate the role of adiposity from that of ageing in this process. We performed oral glucose tolerance tests and determined overall and tissue-specific glucose utilization under euglycemic-hyper-insulinemic conditions in 3-, 8-, and 24-month-old rats fed ad libitum, and in 8- and 24-month-old rats after 3 months of calorie restriction. Body composition and adipocyte-derived cytokines such as leptin, resistin, and adiponectin were analyzed. Overall insulin sensitivity decreases with ageing. Calorie restriction improves global insulin sensitivity in 8- but not in 24-month-old rats. Insulin-stimulated glucose utilization in adipose tissues decreases in 8 months, while in oxidative muscles it reaches significance only in older rats. Calorie restriction restores adipose tissue insulin sensitivity only in 8-month-old rats and no changes are observed in muscles of 24-month-old rats. Resistin and leptin increase with ageing. Food restriction lowers resistin and increases adiponectin in 8-month-old rats and decreases leptin in both ages. Visceral and total fat increase with ageing and decrease after calorie restriction. We conclude that accretion of visceral fat plays a key role in the development of insulin resistance after sexual maturity, which is reversible by calorie restriction. With aging, accumulation of retroperitoneal and total body fat leads to impaired muscle glucose uptake and to a state of insulin resistance that is difficult to reverse.

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