Changes in food intake, metabolic parameters and insulin resistance are induced by an isoenergetic, medium-chain fatty acid diet and are associated with modifications in insulin signalling in isolated rat pancreatic islets
2013
Marçal, A. C. | Camporez, J. P. G. | Lima-Salgado, T. M. | Cintra, D. E. | Akamine, E. H. | Ribeiro, L. M. | Almeida, F. N. | Zanuto, R. P. | Curi, R. | Boldrini, S. C. | Liberti, E. A. | Fiamoncini, J. | Hirabara, S. M. | Deschamps, F. C. | Carpinelli, A. R. | Carvalho, C. R. O.
Long-chain fatty acids are capable of inducing alterations in the homoeostasis of glucose-stimulated insulin secretion (GSIS), but the effect of medium-chain fatty acids (MCFA) is poorly elucidated. In the present study, we fed a normoenergetic MCFA diet to male rats from the age of 1 month to the age of 4 months in order to analyse the effect of MCFA on body growth, insulin sensitivity and GSIS. The 45 % MCFA substitution of whole fatty acids in the normoenergetic diet impaired whole body growth and resulted in increased body adiposity and hyperinsulinaemia, and reduced insulin-mediated glucose uptake in skeletal muscle. In addition, the isolated pancreatic islets from the MCFA-fed rats showed impaired GSIS and reduced protein kinase Bα (AKT₁) protein expression and extracellular signal-related kinase isoforms 1 and 2 (ERK₁/₂) phosphorylation, which were accompanied by increased cellular death. Furthermore, there was a mildly increased cholinergic sensitivity to GSIS. We discuss these findings in further detail, and advocate that they might have a role in the mechanistic pathway leading to the compensatory hyperinsulinaemic status found in this animal model.
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