Differential effects of insulin resistance on leucine and glucose kinetics in obesity

The effects of insulin resistance on glucose and amino acid metabolism were studied in obese nondiabetic women (body mass index [BMI], (32.8 +/- 2) and in lean controls. Glucose disposal rate, hepatic glucose production, and leucine carbon flux and oxidation were simultaneously measured during the postabsorptive state and during euglycemic hyperinsulinemia, by means of primed, constant infusions of D-[6,6-2H2]glucose and L-[1-13C]leucine. Each subject participated in two insulin clamp studies on separate days, at infusion rates of 10 and 40 mU (m2.min)-1, producing plasma insulin levels of 20 to 25 and 70 to 80 microU/mL, respectively. Fat-free mass (FFM) was calculated from underwater weighing measurements. Insulin-mediated glucose disposal rate was significantly slower in the obese group: 2.05 +/- 0.05 versus 3.84 +/- 0.18 mg (kg.min)-1 in controls during the 10-mU insulin clamp, and 3.80 +/- 0.23 versus 9.16 +/- 0.47 mg (kg.min)-1 during the 40-mU clamp. The insulin-induced decrease in plasma levels of branched chain amino acids was also significantly blunted in the obese group. Baseline leucine flux was similar in lean and obese subjects (78 +/- 3 and 71 +/- 2 mumol (kg.h)-1, respectively), and its decline in response to insulin infusion was also comparable (8% and 10% during the 10-mU/m2 clamp, and of 17% and 18% during the 40-mU/m2 clamp in lean and obese, respectively). Basal leucine carbon oxidation (from [13C]leucine and [13C]alpha ketoisocaproate [alpha-KIC] plasma enrichments) was also similar in lean and obese, and did not change significantly with insulin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)