Whey protein, but not leucine ingestion reduces insulin sensitivity (1161.5)

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/m 2 body surface area/min) in two groups (n = 9/group) of women (age: 58±1 yr, BMI: 35±1 kg/m 2 ) 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. Grant Funding Source : Supported by grants from the NIH and an Ajinomoto Exploratory Research Grant.