title: Oral administration of leucine stimulates phosphorylation of 4E-bP1 and S6K 1 in skeletal muscle but not in liver of diabetic rats.
abstract: Leucine performs a signaling role to enhance protein synthesis by phosphorylating eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) and 70-kDa ribosomal protein S6 kinase (S6K1), two key regulatory proteins involved in the initiation of mRNA translation. The purpose of the current study was to assess whether the phosphorylation of 4E-BP1 and S6K1 was increased in skeletal muscle and liver by an oral administration of leucine to diabetic rats and to determine the in vivo contribution of insulin to a leucine-dependent induction of 4E-BP1 and S6K1 phosphorylation. Food-deprived (18 h) normal and diabetic rats were orally administered 135 mg/ 100 g body weight L-leucine and sacrificed at 1 h after administration. Leucine administration resulted in enhanced phosphorylation of 4E-BP1 and S6K1 in skeletal muscle and in liver of nondiabetic rats. The stimulatory action of leucine on the phosphorylation of 4E-BP1 and S6K1 in skeletal muscle was not abolished in rats with streptozotocin-induced diabetes. In contrast, leucine administration did not stimulate the phosphorylation of 4E-BP1 and S6K1 in the liver of diabetic rats. These findings suggest that in skeletal muscle, leucine functions as a nutritional signaling molecule that independently regulates the phosphorylation states of 4E-BP1 and S6K1. In contrast to skeletal muscle, insulin is essential in mediating the leucine-dependent induction of 4E-BP1 and S6K1 phosphorylation in liver. leucine, 4E-BP1, S6K1, translation initiation, diabetes
authors.affiliation: Department of Animal Science, Faculty of Agriculture, Utsunomiya University, Tochigi, Japan. fumiaki@cc.utsunomiya-u.ac.jp
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Yoshizawa
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Hirayama
authors.forename: Haruhito
authors.initials: H
authors.lastname: Sekizawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagasawa
authors.forename: Kunio
authors.initials: K
authors.lastname: Sugahara
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000139:chemically induced*; D007328:Insulin / Q000097:blood*; D047908:Intracellular Signaling Peptides and Proteins; D007930:Leucine / Q000008:administration & dosage*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D010750:Phosphoproteins / Q000187:drug effects* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D019893:Ribosomal Protein S6 Kinases / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D002352:Carrier Proteins; C499526:Eif4ebp1 protein, rat; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D019893:Ribosomal Protein S6 Kinases; D007930:Leucine