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 specific activity as plasma [radioactive infused glucose (hot-GINF) method]. Alternatively, a second tracer can be used to measure the effective volume of glucose [variable-pV method of Issekutz (T. Issekutz, R. Issekutz, and D. Elahi. (Can. J. Physiol. 52:215-224, 1974)]. To determine whether these techniques provide concordant assessments of insulin action under non-steady-state conditions, glucose turnover was measured in six subjects. After initiation of insulin (0.6 mU.kg-1 x min-1), both methods indicated similar rates of suppression of hepatic glucose release, which was complete by approximately 100-120 min. In contrast, the traditional fixed-pV method of Steele (R. Steele, J. Wall, R. DeBodo, and N. Altszuler. Am. J. Physiol. 187:15-24 1956) underestimated turnover (P < 0.01) resulting in apparent complete suppression of glucose release within approximately 40 min (P < 0.01 vs. other methods). The hot-GINF and variable-pV methods also yielded similar estimates of turnover after discontinuation of insulin. Both indicated that resumption of hepatic glucose release was slower (P < 0.01) and fall of glucose uptake faster (P < 0.01) than suggested by the fixed-pV method. 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.
Butler
P C
PC
Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905.
Caumo
A
A
Zerman
A
A
O'Brien
P C
PC
Cobelli
C
C
Rizza
R A
RA
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008433:Mathematics; D008954:Models, Biological; D011865:Radioisotope Dilution Technique; D012016:Reference Values; D013997:Time Factors; D014316:Tritium
D001786:Blood Glucose; D002250:Carbon Radioisotopes; D007328:Insulin; D014316:Tritium; D005934:Glucagon; D005947:Glucose