METHODS FOR ASSESSMENT OF THE RATE OF ONSET AND OFFSET OF INSULIN ACTION DURING NONSTEADY STATE IN HUMANS

Measurement of glucose turnover under non-steady-state conditions has proven problematic. When the mass of the glucose pool is not changing (i.e., glucose concentrations are constant) non-steady-state error can be minimized if all glucose entering the circulation has the same spe cific activity as plasma [radioactive infused glucose (hot-GINF) metho d]. Alternatively, a second tracer can be used to measure the effectiv e volume of glucose [variable-pV method of Issekutz (T. Issekutz, R. I ssekutz, and D. Elahi. (Can. J. Physiol. 52: 215-224, 1974) ]. To dete rmine whether these techniques provide concordant assessments of insul in action under non-steady-state conditions, glucose turnover was meas ured in six subjects. After initiation of insulin (0.6 mU . kg- 1 . mi n- 1), both methods indicated similar rates of suppression of hepatic glucose release, which was complete by approximately 100-120 min. In c ontrast, the traditional fixed-pV method of Steele (R. Steele, J. Wall , R. DeBodo, and N. Altszuler. Am. J. Physiol. 187: 15-24 1956) undere stimated turnover (P < 0.01) resulting in apparent complete suppressio n of glucose release within approximately 40 min (P < 0.01 vs. other m ethods). The hot-GINF and variable-pV methods also yielded similar est imates of turnover after discontinuation of insulin. Both indicated th at resumption of hepatic glucose release was slower (P < 0.01) and fal l of glucose uptake faster (P < 0.01) than suggested by the fixed-pV m ethod. Thus both the hot-GINF and variable-pV methods avoid non-steady -state error introduced by the fixed-pV method and provide concordant assessments of the rate of onset and offset of insulin action.