Protein ingestion induces muscle insulin resistance independent of leucine-mediated mTOR activation
Research output: Contribution to journal › Journal article › Research › peer-review
Increased plasma branched-chain amino acid concentrations are associated with insulin resistance, and intravenous amino acid infusion blunts insulin-mediated glucose disposal. We tested the hypothesis that protein ingestion impairs insulin-mediated glucose disposal by leucine-mediated mTOR signaling, which can inhibit AKT. We measured glucose disposal and muscle p-mTORSer2448, p-AKTSer473, and p-AKTThr308 in 22 women during a hyperinsulinemic-euglycemic clamp procedure with and without concomitant ingestion of whey protein (0.6 g/kg fat-free mass; n = 11) or leucine that matched the amount given with whey protein (n = 11). Both whey protein and leucine ingestion raised plasma leucine concentration by approximately twofold and muscle p-mTORSer2448 by ∼30% above the values observed in the control (no amino acid ingestion) studies; p-AKTSer473 and p-AKTThr308 were not affected by whey protein or leucine ingestion. Whey protein ingestion decreased insulin-mediated glucose disposal (median 38.8 [quartiles 30.8, 61.8] vs. 51.9 [41.0, 77.3] µmol glucose/µU insulin · mL-1 · min-1; P < 0.01), whereas ingestion of leucine did not (52.3 [43.3, 65.4] vs. 52.3 [43.9, 73.2]). These results indicate that 1) protein ingestion causes insulin resistance and could be an important regulator of postprandial glucose homeostasis and 2) the insulin-desensitizing effect of protein ingestion is not due to inhibition of AKT by leucine-mediated mTOR signaling.
Original language | English |
---|---|
Journal | Diabetes |
Volume | 64 |
Issue number | 5 |
Pages (from-to) | 1555-1563 |
Number of pages | 9 |
ISSN | 0012-1797 |
DOIs | |
Publication status | Published - 2015 |
Externally published | Yes |
Bibliographical note
© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
- Aged, Amino Acids/blood, Blood Glucose, Dietary Proteins/administration & dosage, Female, Glucose Clamp Technique, Humans, Insulin/blood, Insulin Resistance/physiology, Leucine/metabolism, Middle Aged, Milk Proteins/pharmacology, Muscle, Skeletal/physiology, Signal Transduction, TOR Serine-Threonine Kinases/genetics, Whey Proteins
Research areas
ID: 289962831