Studies on the relationship between insulin concentrations and insulin action

The relationship between insulin concentrations and insulin effects was assessed using a 30-min steady-state perfusion of insulin across the human forearm and a 90-min recovery period in 17 normal men. During perfusion, calculated insulin increments in forearm arterial plasma insulin were 87 +/- 4 (group I), 161 +/- 17 (group II), and 333 +/- 55 microU/ml (group III), respectively. Measured venous insulin increments were 33 +/- 4, 66 +/- 6, and 231 +/- 27 microU/ml. During perfusion, venous and arterial increments were linearly related (r = 0.88, P less than 0.001). With discontinuation of perfusion, venous increments of insulin became undetectable after 15 min in groups I and II, and after 30 min in group III. Of the total microunits of insulin perfused, 46.0 +/- 11.0%, 45.3 +/- 9.4%, and 36.5 +/- 4.8%, respectively, remained unaccounted for 90 min after perfusion. Effects of insulin on arteriovenous differences of FFA and potassium persisted throughout the recovery period, with peak effects occurring after perfusion for all groups. Estimated interstitial insulin levels in the three groups fell below 10 microU/ml by 45, 60, and 90 min after perfusion, respectively. Although peripheral tissues had a significant capacity to sequester insulin, the persistence of biologic effects was not consistent with increased concentrations within the interstitial spaces. Effects of insulin upon glucose waned first, followed by effects upon potassium and then lipolysis.