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Chronic caffeine intake reverses age-induced insulin resistance in the rat: effect on skeletal muscle Glut4 transporters and AMPK activity

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Abstract

The role of caffeine consumption on insulin action is still under debate. The hypothesis that chronic caffeine intake reverses aging-induced insulin resistance in the rat was tested in this work. The mechanism by which caffeine restores insulin sensitivity was also investigated. Six groups of rats were used: 3 months old (3 M), 3 months old caffeine-treated (3MCaf), 12 months old (12 M), 12 months old caffeine-treated (12MCaf), 24 months old (24 M), and 24 months old caffeine-treated (24MCaf). Caffeine was administered in drinking water (1 g/l) during 15 days. Insulin sensitivity was assessed by means of the insulin tolerance test. Blood pressure, body weight, visceral and total fat, fasting glycemia and insulinemia, plasma nonesterified fatty acids (NEFA), total antioxidant capacity (TAC), cortisol, nitric oxide, and catecholamines were monitored. Skeletal muscle Glut4 and 5′-AMP activated protein kinase (AMPK) protein expression and activity were also assessed. Aged rats exhibited diminished insulin sensitivity accompanied by hyperinsulinemia and normoglycemia, increased visceral and total fat, decreased TAC and plasma catecholamines, and also decreased skeletal muscle Glut4 and AMPK protein expression. Chronic caffeine intake restored insulin sensitivity and regularized circulating insulin and NEFA in both aging models. Caffeine neither modified skeletal muscle AMPK expression nor activity in aged rats; however, it decreased visceral and total fat in 12 M rats and it restored skeletal muscle Glut4 expression to control values in 24 M rats. We concluded that chronic caffeine intake reverses aging-induced insulin resistance in rats by decreasing NEFA production and also by increasing Glut4 expression in skeletal muscle.

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Acknowledgments

We are very grateful to Elena Gonzalez Muñoz and Constancio Gonzalez from the Faculty of Medicine of the University of Valladolid for the serum catecholamines quantification. We also thank to Inês Faustino for her technical support and to Dr. Michael Bright for reviewing the English. The work was financially supported by L’Oreal-Unesco-FCT Awards for Women in Science 2009-Portugal and by Portuguese Foundation for Science and Technology grant PTDC/SAU-ORG/111417/2009. There are no conflicts of interest.

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  1. CEDOC, Departamento de Fisiopatologia, Faculdade de Ciências Médicas, NOVA, Lisbon, Portugal

    Maria P. Guarino

  2. CEDOC, Departamento de Farmacologia, Faculdade de Ciências Médicas, NOVA, Campo Mártires da Pátria, 130, 1169-056, Lisbon, Portugal

    Maria J. Ribeiro, Joana F. Sacramento & Sílvia V. Conde

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  1. Maria P. Guarino
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  4. Sílvia V. Conde
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Correspondence to Sílvia V. Conde.

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Guarino, M.P., Ribeiro, M.J., Sacramento, J.F. et al. Chronic caffeine intake reverses age-induced insulin resistance in the rat: effect on skeletal muscle Glut4 transporters and AMPK activity. AGE 35, 1755–1765 (2013). https://doi.org/10.1007/s11357-012-9475-x

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