Methods for assessment of the rate of onset and offset of insulin action during nonsteady state in humans

P. C. Butler, A. Caumo, A. Zerman, P. C. O'Brien, C. Cobelli, R. A. Rizza

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49 Scopus citations


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 · min-1), both methods indicated similar rates of suppression of hepatic glucose release, which was complete by ~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 ~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.

Original languageEnglish (US)
Pages (from-to)E548-E560
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number4 27-4
StatePublished - 1993


  • activation
  • deactivation
  • glucose turnover
  • hepatic glucose release
  • non-steady-state error

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


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