title: High insulin combined with essential amino acids stimulates skeletal muscle mitochondrial protein synthesis while decreasing insulin sensitivity in healthy humans.
abstract: BACKGROUND
  Insulin and essential amino acids (EAAs) regulate skeletal muscle protein synthesis, yet their independent effects on mitochondrial protein synthesis (MiPS) and oxidative function remain to be clearly defined.
  
  
  OBJECTIVE
  The purpose of this study was to determine the effects of high or low insulin with or without EAAs on MiPS.
  
  
  METHODS
  Thirty participants were randomized to 3 groups of 10 each with each participant studied twice. Study groups comprised (1) low and high insulin, (2) low insulin with and without EAAs, and (3) high insulin with and without EAAs.
  
  
  METHODS
  The study was conducted in an in-patient clinical research unit.
  
  
  METHODS
  Eligible participants were 18 to 45 years old, had a body mass index of <25 kg/m(2), and were free of diseases and medications that might impair mitochondrial function.
  
  
  METHODS
  Low (∼ 6 μU/mL) and high (∼ 40 μU/mL) insulin levels were maintained by iv insulin infusion during a somatostatin clamp while maintaining euglycemia (4.7-5.2 mM) and replacing GH and glucagon. The EAA infusion was 5.4% NephrAmine. l-[ring-(13)C6]Phenylalanine was infused, and muscle needle biopsies were performed.
  
  
  RESULTS
  Muscle MiPS, oxidative enzymes, and plasma amino acid metabolites were measured.
  
  
  RESULTS
  MiPS and oxidative enzyme activities did not differ between low and high insulin (MiPS: 0.07 ± 0.009 vs 0.07 ± 0.006%/h, P = .86) or between EAAs and saline during low insulin (MiPS: 0.05 ± 0.01 vs 0.07 ± 0.01, P = .5). During high insulin, EAAs in comparison with saline increased MiPS (0.1 ± 0.01 vs 0.06 ± 0.01, P < .05) and cytochrome c oxidase activity (P < .05) but not citrate synthase (P = .27). EAA infusion decreased (P < .05) the glucose infusion rates needed to maintain euglycemia during low (∼ 40%) and high insulin (∼ 24%).
  
  
  CONCLUSIONS
  EAAs increased MiPS and oxidative enzyme activity only with high insulin concentrations.
authors.affiliation: Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Robinson
authors.forename: Mattias
authors.initials: M
authors.lastname: Soop
authors.forename: Tae Seo
authors.initials: TS
authors.lastname: Sohn
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Morse
authors.forename: Jill M
authors.initials: JM
authors.lastname: Schimke
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Klaus
authors.forename: K Sreekumaran
authors.initials: KS
authors.lastname: Nair
mesh_terms: D000293:Adolescent; D000328:Adult; D000601:Amino Acids, Essential / Q000378:metabolism / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000378:metabolism; D010649:Phenylalanine / Q000097:blood / Q000494:pharmacology; D013004:Somatostatin / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000601:Amino Acids, Essential; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D009124:Muscle Proteins; D010649:Phenylalanine; D013004:Somatostatin