Protein Ingestion Induces Muscle Insulin Resistance Independent of Leucine-Mediated mTOR Activation.

Abstract

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-mTOR(Ser2448), p-AKT(Ser473), and p-AKT(Thr308) 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-mTOR(Ser2448) by ∼30% above the values observed in the control (no amino acid ingestion) studies; p-AKT(Ser473) and p-AKT(Thr308) 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.

• Authors: Gordon I Smith, Jun Yoshino, Kelly L Stromsdorfer, Seth J Klein, Faidon Magkos, Dominic N Reeds, Samuel Klein, Bettina Mittendorfer
• Journal: Diabetes (Diabetes) Vol. 64 Issue 5 Pg. 1555-63 (May 2015) ISSN: 1939-327X [Electronic] United States
• PMID: 25475435 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: © 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.

Chemical References

• Amino Acids
• Blood Glucose
• Dietary Proteins
• Insulin
• Milk Proteins
• Whey Proteins
• MTOR protein, human
• TOR Serine-Threonine Kinases
• Leucine

Topics

• Aged
• Amino Acids (blood, metabolism)
• Blood Glucose
• Dietary Proteins (administration & dosage, pharmacology)
• Female
• Glucose Clamp Technique
• Humans
• Insulin (blood, metabolism)
• Insulin Resistance (physiology)
• Leucine (metabolism)
• Middle Aged
• Milk Proteins (pharmacology)
• Muscle, Skeletal (physiology)
• Signal Transduction
• TOR Serine-Threonine Kinases (genetics, metabolism)
• Whey Proteins