Protein ingestion induces muscle insulin resistance independent of leucine-mediated mTOR activation
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Protein ingestion induces muscle insulin resistance independent of leucine-mediated mTOR activation. / Smith, Gordon I; Yoshino, Jun; Stromsdorfer, Kelly L; Klein, Seth J; Magkos, Faidon; Reeds, Dominic N; Klein, Samuel; Mittendorfer, Bettina.
In: Diabetes, Vol. 64, No. 5, 2015, p. 1555-1563.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Protein ingestion induces muscle insulin resistance independent of leucine-mediated mTOR activation
AU - Smith, Gordon I
AU - Yoshino, Jun
AU - Stromsdorfer, Kelly L
AU - Klein, Seth J
AU - Magkos, Faidon
AU - Reeds, Dominic N
AU - Klein, Samuel
AU - Mittendorfer, Bettina
N1 - © 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.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Aged
KW - Amino Acids/blood
KW - Blood Glucose
KW - Dietary Proteins/administration & dosage
KW - Female
KW - Glucose Clamp Technique
KW - Humans
KW - Insulin/blood
KW - Insulin Resistance/physiology
KW - Leucine/metabolism
KW - Middle Aged
KW - Milk Proteins/pharmacology
KW - Muscle, Skeletal/physiology
KW - Signal Transduction
KW - TOR Serine-Threonine Kinases/genetics
KW - Whey Proteins
U2 - 10.2337/db14-1279
DO - 10.2337/db14-1279
M3 - Journal article
C2 - 25475435
VL - 64
SP - 1555
EP - 1563
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 5
ER -
ID: 289962831