ACUTE NORADRENERGIC ACTIVATION INDUCES INSULIN-RESISTANCE IN HUMAN SKELETAL-MUSCLE

We assessed in normal subjects the effects of an acute increase in for earm norepinephrine (NE) release, evoked by - 20 mmHg lower body negat ive pressure (LBNP), on insulin-mediated muscle glucose uptake. Seven normal subjects underwent the following two insulin euglycemic clamps in random sequence: one during application of LBNP and the other witho ut LBNP (control study). In the control study, hyperinsulinemia (appro ximate to 60 mu U/ml) produced a significant increment in forearm NE r elease, measured by using the forearm perfusion technique combined wit h infusion of tritiated NE (from 4.91 i 1 to 7.94 +/- 1.33 ng.l(-1).mi n(-1); P < 0.05). Forearm glucose uptake rose from 0.97 +/- 0.13 to 5. 2 +/- 0.2 mg.l(-1).min(-1) in response to insulin infusion. When the i nsulin clamp was performed during LBNP, forearm NE release rose to sig nificantly higher values than those of the control study !from 4.33 +/ - 0.52 to 12.7 +/- 1.46 ng.l(-1).min(-1); P < 0.01 vs. control). Under these conditions, the stimulatory effect of insulin on forearm glucos e uptake was markedly reduced (from 0.78 +/- 0.10 to 3.2 +/- 0.7 mg.l( -1).min(-1); P < 0.02 vs. control). Forearm blood flow and plasma epin ephrine and free fatty acid concentrations were comparable in the two study sessions. These data demonstrate that an acute activation of end ogenous NE release antagonizes insulin-mediated glucose uptake in fore arm skeletal muscle, probably accounted for by a direct metabolic effe ct of NE.