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 glu-cose, but can be compensated for by abundant amino acid (AA) provision. This effect and its mec hanismwere sought in obesity. Methods: Pancreatic clamps were performed in 8 lean and 11 obese men, following 5-h pos tabsorptive,3-h infusions of octreotide, basal glucagon, and growth hormone, with clamped postprandial-level insulin,glucose, and AA. Whole-body [1-13C]-leucine and [3-3H]-glucose kinetics, skeletal muscle protein(2H5-phenylalanine) fractional synthesis rates, and insulin signaling were determined. Results: Clamp D insulin and D branched-chain AA did not differ; fasting glucagon and growth hormonewere maintained. Glucose uptake was 20% less in obese concurrent with less AktSer473, but also lessIRS-1Ser636/639phosphoryla tion. Stimulation of whole-body, myofibrillar, and sarcoplasmic protein synthe-sis was similar. Whole-body protein catabolism suppression tended to be less (P50.06), resulting inlesser net balance (1.09 6 0.07 vs. 1.31 6 0.08 lmol [kg FFM21]min21, P 5 0.048). Increments in muscleS6K1Thr389phosphorylation were less in the obese, but 4E-BP1Ser65did not differ. Conclusions: Hy peraminoacidemia with hyperinsulinemia stimulated protei n synthesis (possibly via nutrientsignaling) normally in obesity, but suppression of proteolysis ma y be compro mised. Whether long-term highprotein intakes could compensate for the insu lin resistance of protein anabolism remains to be determined