The Antilipolytic Action of Insulin in Obese Subjects with Resistance to Its Glucoregulatory Action*

To compare the ability of insulin to regulate lipolysis in lean and obese subjects, free fatty acid (FFA) suppression was compared in groups of six lean body mass index, 25.7 ± 1.1 (±SEM) kg/m2 and six obese (body mass index, 48.8 ± 3.1) Pima Indians during euglycemic hyperinsulinemic clamps which increased plasma insulin levels approximatley 10, 20, and 100µ U/ml above basal concentrations. Basal FFA concentrations were slightly, but not significantly, elevated inthe obese group (445 ± 35 vs. 406 ± 40 µeq/liter). The mean decline in FFA from basal after 60–90 min of insulin infusion in the obese group was somewhat less than that in the lean group at the lower doses 67 ± 23 vs. 132 ± 32 (P = NS) during the 10-μU clamp, and 144 ± 39 vs. 217 ± 20 (P = NS) during the 20-μU clamp and was almost identical in the two groups during the 100-μU clamp (226 ± 29 vs. 229 ± 51). In contrast, insulin-mediated glucose disposal at all insulin increments was much lower in the obese group (0.33 ± 0.03, 0.56 ± 0.04, and 1.39 ± 0.04 mg/kgmin) than in the lean group (0.78 ± 0.06, 1.67 ± 0.12, and 4.96 ± 0.26; P < 0.001). The data suggest that although the obese subjects exhibited significant resistance to the glucoregulatory action of insulin, there were only small changes in insulin′s antilipolytic effects. Relative maintenance of sensitivity to the antilipolytic action of insulin in the presence of resistance to insulin′s glucoregulatory action could maintain fat deposition in obese individuals.