Relationship between insulin-mediated glucose disposal by muscle and adipose tissue lipolysis in healthy volunteers.

Abstract

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 micrograms/h), insulin (25 mU/m2min), and glucose (240 mg/m2.min)]. On another occasion, plasma FFA and glycerol concentrations were determined at the end of 3 sequential infusion periods (IP): IP1, somatostatin (350 micrograms/h) plus basal insulin replacement (5 mU/m2.min); IP2, somatostatin (350 micrograms/h), insulin (5 mU/m2.min), and isoproterenol (270 ng/m2.min); and IP3, somatostatin (350 micrograms/h), isoproterenol (270 ng/m2.min), and insulin (10 mU/m2.min). SSPG concentrations correlated with FFA concentrations 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 = 0.70; P < 0.01; IP3: r = 0.65; P < 0.02). Correlations between SSPG and glycerol concentrations were also highly statistically significant (IP1: r = 0.62; P < 0.03; IP2: r = 0.65; P < 0.02; IP3: r = 0.70; 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.