title: Protein and glucose metabolic responses to hyperinsulinemia, hyperglycemia, and hyperaminoacidemia in obese men.
abstract: OBJECTIVE
  In insulin-resistant states, resistance of protein anabolism occurs concurrently with that of glucose, but can be compensated for by abundant amino acid (AA) provision. This effect and its mechanism were sought in obesity.
  
  
  METHODS
  Pancreatic clamps were performed in 8 lean and 11 obese men, following 5-h postabsorptive, 3-h infusions of octreotide, basal glucagon, and growth hormone, with clamped postprandial-level insulin, glucose, and AA. Whole-body [1-(13) C]-leucine and [3-(3) H]-glucose kinetics, skeletal muscle protein ((2) H5 -phenylalanine) fractional synthesis rates, and insulin signaling were determined.
  
  
  RESULTS
  Clamp Δ insulin and Δ branched-chain AA did not differ; fasting glucagon and growth hormone were maintained. Glucose uptake was 20% less in obese concurrent with less Akt(Ser473) , but also less IRS-1(Ser636/639) phosphorylation. Stimulation of whole-body, myofibrillar, and sarcoplasmic protein synthesis was similar. Whole-body protein catabolism suppression tended to be less (P=0.06), resulting in lesser net balance (1.09 ± 0.07 vs. 1.31 ± 0.08 μmol [kg FFM(-1) ] min(-1) , P=0.048). Increments in muscle S6K1(Thr389) phosphorylation were less in the obese, but 4E-BP1(Ser65) did not differ.
  
  
  CONCLUSIONS
  Hyperaminoacidemia with hyperinsulinemia stimulated protein synthesis (possibly via nutrient signaling) normally in obesity, but suppression of proteolysis may be compromised. Whether long-term high protein intakes could compensate for the insulin resistance of protein anabolism remains to be determined.
authors.affiliation: Crabtree Nutrition Laboratories, Department of Medicine, McGill University, and Research Institute of the McGill University Health Centre, Montreal, Quebec City, Canada.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Chevalier
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Burgos
authors.forename: José A
authors.initials: JA
authors.lastname: Morais
authors.forename: Réjeanne
authors.initials: R
authors.lastname: Gougeon
authors.forename: Maya
authors.initials: M
authors.lastname: Bassil
authors.forename: Marie
authors.initials: M
authors.lastname: Lamarche
authors.forename: Errol B
authors.initials: EB
authors.lastname: Marliss
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000378:metabolism*; D005934:Glucagon / Q000008:administration & dosage / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000097:blood; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D006946:Hyperinsulinism / Q000378:metabolism*; D007262:Infusions, Intravenous; D007328:Insulin / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D015282:Octreotide / Q000008:administration & dosage; D010179:Pancreas / Q000378:metabolism; D019518:Postprandial Period; D055815:Young Adult
chemical_list: D000596:Amino Acids; D007328:Insulin; D009124:Muscle Proteins; D019382:Human Growth Hormone; D005934:Glucagon; D005947:Glucose; D015282:Octreotide