title: 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.
abstract: 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 Ba (AKT1) protein expression and extracellular signal-related kinase isoforms 1 and 2 (ERK(1/2)) 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.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, 05508-900 São Paulo, SP, Brazil. acmarcal@yahoo.com.br
authors.forename: A C
authors.initials: AC
authors.lastname: Marçal
authors.forename: J P G
authors.initials: JP
authors.lastname: Camporez
authors.forename: T M
authors.initials: TM
authors.lastname: Lima-Salgado
authors.forename: D E
authors.initials: DE
authors.lastname: Cintra
authors.forename: E H
authors.initials: EH
authors.lastname: Akamine
authors.forename: L M
authors.initials: LM
authors.lastname: Ribeiro
authors.forename: F N
authors.initials: FN
authors.lastname: Almeida
authors.forename: R P
authors.initials: RP
authors.lastname: Zanuto
authors.forename: R
authors.initials: R
authors.lastname: Curi
authors.forename: S C
authors.initials: SC
authors.lastname: Boldrini
authors.forename: E A
authors.initials: EA
authors.lastname: Liberti
authors.forename: J
authors.initials: J
authors.lastname: Fiamoncini
authors.forename: S M
authors.initials: SM
authors.lastname: Hirabara
authors.forename: F C
authors.initials: FC
authors.lastname: Deschamps
authors.forename: A R
authors.initials: AR
authors.lastname: Carpinelli
authors.forename: C R O
authors.initials: CR
authors.lastname: Carvalho
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000378:metabolism*; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood* / Q000737:chemistry
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D014280:Triglycerides; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C