Abstract
We determined the effects of intravenous infusion of amino acids (AA) at serum insulin of 5, 30, 72, and 167 mU/l on anabolic signaling, expression of ubiquitin-proteasome components, and protein turnover in muscles of healthy young men. Tripling AA availability at 5 mU/l insulin doubled incorporation of [1-C-13] leucine [i.e., muscle protein synthesis ( MPS), P < 0.01] without affecting the rate of leg protein breakdown (LPB; appearance of d(5)-phenylalanine). While keeping AA availability constant, increasing insulin to 30 mU/l halved LPB (P < 0.05) without further inhibition at higher doses, whereas rates of MPS were identical to that at 5 mU/l insulin. The phosphorylation of PKB Ser(473) and (p)70(S6k) Thr(389) increased concomitantly with insulin, but whereas raising insulin to 30 mU/l increased the phosphorylation of mTOR Ser(2448), 4E-BP1 Thr(37/46), or GSK3 beta Ser(9) and decreased that of eEF2 Thr(56), higher insulin doses to 72 and 167 mU/l did not augment these latter responses. MAFbx and proteasome C2 subunit proteins declined as insulin increased, with MuRF-1 expression largely unchanged. Thus increasing AA and insulin availability causes changes in anabolic signaling and amounts of enzymes of the ubiquitin-proteasome pathway, which cannot be easily reconciled with observed effects on MPS or LPB.
Original language | English |
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Pages (from-to) | E595-E604 |
Number of pages | 10 |
Journal | American Journal of Physiology: Endocrinology and Metabolism |
Volume | 295 |
Issue number | 3 |
Early online date | 24 Jun 2008 |
DOIs | |
Publication status | Published - Sept 2008 |
Keywords
- muscle protein synthesis
- muscle protein breakdown
- human skeletal-muscle
- physiological hyperinsulinemia
- euglycemic hyperinsulinemia
- human forearm
- healthy man
- whole-body
- proteolysis
- availability
- metabolism
- infusion