Differential effect of insulin on whole-body proteolysis and glucose metabolism in normal-weight, obese, and reduced-obese women.

The whole-body rate of proteolysis, as indicated by the postabsorptive appearance rate (Ra) of leucine, is increased in obese women. The present study was conducted to examine the hypothesis that the increased proteolysis is explained by insulin resistance, and to determine if proteolysis returns to normal when obese women reduce to normal weight. The mean basal leucine Ra was 21% higher in 31 obese women (> 135% ideal weight) than in 17 normal-weight women, and 9% higher per kilogram lean body mass ([LBM] P > .05). When 17 of the obese women reduced and stabilized at 100% to 116% of ideal weight, their mean basal leucine Ra decreased 17% (7%/kg LBM) and was not significantly different from that of the normal-weight control group. Insulin (40 mU/m2/min) was infused for 2 hours while maintaining euglycemia in eight normal-weight, 14 obese, and eight reduced-obese subjects. Glucose disposal per kilogram LBM was 29% lower in obese than in normal-weight subjects (P < .05) and was normal in the reduced-obese subjects. Insulin suppressed the leucine Ra an average of 18.4% in the control group, 20.4% in the obese group, and 24.1% in the reduced-obese group. Suppression of the leucine Ra by insulin did not correlate with the waist to hip ratio (WHR), glucose disposal rate, or basal leucine Ra. We conclude that the increased basal proteolysis of obese women is reversed by weight loss, and is not caused by insulin resistance.