title: Insulin immuno-neutralization in chicken: effects on insulin signaling and gene expression in liver and muscle.
abstract: In order to evaluate the role of insulin in chicken, an insulin immuno-neutralization was performed. Fed chickens received 1 or 3 i.v. injections of anti-insulin serum (2-h intervals), while fed or fasted controls received normal serum. Measurements included insulin signaling cascade (at 1 h in liver and muscle), metabolic or endocrine plasma parameters (at 1 and 5 h), and qRT-PCR analysis (at 5 h) of 23 genes involved in endocrine regulation, metabolisms, and transcription. Most plasma parameters and food intake were altered by insulin privation as early as 1 h and largely at 5 h. The initial steps of insulin signaling pathways including insulin receptor (IR), IR substrate-1 (IRS-1), and Src homology collagen and downstream elements: phosphatidylinositol 3-kinase (PI3K), Akt, GSK3, ERK2, and S6 ribosomal protein) were accordingly turned off in the liver. In the muscle, IR, IRS-1 tyrosine phosphorylation, and PI3K activity remained unchanged, whereas several subsequent steps were altered by insulin privation. In both tissues, AMPK was not altered. In the liver, insulin privation decreased Egr1, PPAR gamma, SREBP1, THRSP alpha (spot 14), D2-deiodinase, glucokinase (GK), and fatty acid synthase (whereas D3-deiodinase and IGF-binding protein 1 transcripts were up-regulated. Liver SREBP1 and GK and plasma IGFBP1 proteins were accordingly down- and up-regulated. In the muscle, PPAR beta delta and atrogin-1 mRNA increased and Egr1 mRNA decreased. Changes in messengers were partly mimicked by fasting. Thus, insulin signaling in muscle is peculiar in chicken and is strictly dependent on insulin in fed status. The 'diabetic' status induced by insulin immuno-neutralization is accompanied by impairments of glucagon secretion, thyroid axis, and expression of several genes involved in regulatory pathways or metabolisms, evidencing pleiotropic effects of insulin in fed chicken.
authors.affiliation: PRC (UMR 6175), INRA, 37380 Nouzilly, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Dupont
authors.forename: Sophie
authors.initials: S
authors.lastname: Tesseraud
authors.forename: Michel
authors.initials: M
authors.lastname: Derouet
authors.forename: Anne
authors.initials: A
authors.lastname: Collin
authors.forename: Nicole
authors.initials: N
authors.lastname: Rideau
authors.forename: Sabine
authors.initials: S
authors.lastname: Crochet
authors.forename: Estelle
authors.initials: E
authors.lastname: Godet
authors.forename: Estelle
authors.initials: E
authors.lastname: Cailleau-Audouin
authors.forename: Sonia
authors.initials: S
authors.lastname: Métayer-Coustard
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Duclos
authors.forename: Christian
authors.initials: C
authors.lastname: Gespach
authors.forename: Tom E
authors.initials: TE
authors.lastname: Porter
authors.forename: Larry A
authors.initials: LA
authors.lastname: Cogburn
authors.forename: Jean
authors.initials: J
authors.lastname: Simon
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D002645:Chickens; D051766:Early Growth Response Protein 1 / Q000235:genetics; D005941:Glucokinase / Q000235:genetics; D007328:Insulin / Q000276:immunology / Q000502:physiology*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics
chemical_list: D051766:Early Growth Response Protein 1; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047495:PPAR gamma; D051780:Sterol Regulatory Element Binding Protein 1; D019869:Phosphatidylinositol 3-Kinases; D005941:Glucokinase; D011972:Receptor, Insulin; D000263:Adenylate Kinase