The present study was performed in 17 nondiabetic subjects and was initiated to determine whether enhanced adipose tissue lipolysis, either basal or catecholamine induced (isoproterenol), and/or resistance to insulin inhibition of isoproterenol-stimulated lipolysis were correlated with resistance to insulin-mediated glucose disposal by muscle. Insulin-mediated glucose disposal was assessed by determining the steady state plasma glucose (SSPG) concentration during the insulin suppression test 180 min infusion of somatostatin (350 (mu)g/h), insulin (25 mU/m(2).min), and glucose (240 mg/m(2).min. On another occasion, plasma FFA and glycerol concentrations were determined at the end of 3 sequential infusion periods (IP): IP1, somatostatin (350 (mu)g/h), insulin (5 mUm(2).min), and isoproterenol (270 ng/m(2).min); and IP3, somatostatin (350 (mu)g/h), isoproterenol (270 ng/m(2).min), and insulin (10 mUm(2).min). SSPG concentrations correlated with FFA concentrationd during all 3 infusion periods after adjustment for age, gender, body mass index, insulin concentration, and ratio of waist to hip girth (IP1: r=0.61; P,0.03; IP2: r=0.07; P<0.01; IP3: r=0.65; P<0.02). Correlations between SPG and glycerol concentrations were also highly statistically significant (IP1: r=0.62; P<0.03; IP2: r=0.65; P<0.02; IP3: r=0.07; P<0.01). These results demonstrate for the first time that plasma FFA and glycerol concentrations are increased commensurate with the degree of resistance to insulin-mediated glucose disposal at a basal insulin level, in response to isoproterenol stimulation, and after insulin inhibition of isoproterenol-stimulated lipolysis.