It is not known whether circulating norepinephrine (NE) has a direct hormonal influence on glucose disposal. This study examines whether moderate elevation of NE alters the disposal of an acute intravenous (IV) glucose load, as analysed by the minimal model of Bergman. Eight healthy normal subjects were infused with either 25 ng/kg/min NE (plasma NE 1,284 +/- 259 pg/mL) or normal saline (plasma NE 314 +/- 86 pg/mL), 30 minutes prior to and during an IV glucose tolerance test (GTT). There was a small but significant rise (P less than .05) in basal blood glucose levels during the initial 30-minute NE infusion which was accompanied by a 40% increase (0.39 +/- .02 to 0.59 +/- .07 nmol/L, P less than .01) in nonesterified fatty acid levels (NEFA). Insulin, C-peptide, and glucagon levels did not change. NE impaired the rate of acute glucose disposal (Kg 1.74 +/- 0.24 v 2.10 +/- 0.23 (min-1, P less than .05). Minimal model analysis revealed a corresponding 35% decrease in insulin sensitivity (SI 4.85 +/- 1.51 v 7.28 +/- 1.16 min-1 microU-1 mL-1 x 10(4), P less than .05) but no significant differences between glucose-mediated glucose disposal or pancreatic B-cell responsiveness. The glucose disposition index (si* phi2), a direct measure of an individual's overall insulin- mediated glucose disposal, was reduced by 70% in the NE-infussed subjects (si* phi2 69 +/-22 v 223 +/- 76 mg-1 ml-1 min-3 x 10(2), p< .05).(ABSTRACT TRUNCATED AT 250 WORDS)