Normal valine disposal in obese subjects with impaired glucose disposal: Evidence for selective insulin resistance

Abstract

Insulin has major effects on both glucose and branched chain amino acid metabolism. To determine whether the insulin resistance of obesity equally affects both glucose and branched chain amino acid metabolism, we measured the ability of obese and normal subjects to dispose of intravenous bolus doses of glucose (25 g) or L-valine (4 g). Basal plasma glucose levels were the same in the 18 normal and 17 obese (163 ± 8% of ideal body weight) subjects, but basal plasma insulin levels were higher in the obese group (15 ± 2 vs 6 ± 1 μU/ml; p < 0.001). The obese group had a slower glucose disappearance rate after glucose challenge (0.84 ± 0.06 vs 1.11 ± 0.07 hr −1; p < 0.01) despite having a greater serum insulin response to the glucose load (26 ± 4 vs 11 ± 1 insulin area units; p < 0.01), confirming insulin resistance. In contrast, disposal of a valine load was the same in normal and obese subjects, as assessed by initial and second phase exponential disappearance rates, metabolic clearance rates of valine, and volumes of distribution. In normal men, disposal rates of glucose and valine after simultaneous administration of both substances were slower than corresponding disposal rates determined when each substance was given alone. We conclude that obese subjects with impaired glucose disposal have normal valine disposal, suggesting that the insulin resistance of obesity can be selective in its effect on different metabolic systems. Glucose and valine also appear to mutually antagonize each other's disposal.