Whey protein, but not leucine ingestion reduces insulin sensitivity

Intravenous infusion of an amino acid mixture reduces insulin-mediated glucose disposal during a hyperinsulinemic-euglycemic clamp. The mechanisms responsible for the adverse effect of amino acids on insulin-mediated glucose disposal are unclear and it is not known whether protein ingestion has similar adverse effects. We hypothesized that protein ingestion impairs insulin-mediated glucose disposal due to leucine-mediated activation of mTOR and serine-phosphorylation of IRS1. To test this hypothesis, we conducted hyperinsulinemic-euglycemic clamps (50 mU insulin/m2 body surface area/min) in two groups (n = 9/group) of women (age: 58±1 yr, BMI: 35±1 kg/m2) who ingested (in randomized order): a) either 0.6 g of whey protein (containing 0.0684 g of leucine) per kg fat-free mass (28.1±1.0 g whey protein total) or placebo or b) 0.0684 g leucine per kg fat-free mass (3.3±0.1 g leucine total) or placebo during the 4-h clamp. Whey protein ingestion significantly reduced the rate of glucose disposal during insulin infusion (2786±324 vs. 3022±383 μmol/min, respectively, P=0.04) whereas leucine ingestion had no effect on insulin-mediated glucose disposal (2787±212 vs. 2805±238 μmol/min, respectively, P=0.90). We conclude that: a) protein ingestion impairs insulin-mediated glucose disposal and b) the insulin desensitizing effect of protein ingestion is not mediated by increased leucine availability.