Dose-response characteristics for effects of insulin on production and utilization of glucose in man.

R. A. Rizza, L. J. Mandarino, J. E. Gerich

Research output: Contribution to journalArticlepeer-review

680 Scopus citations


To determine the dose-response characteristics for the effects of insulin on glucose production, glucose utilization, and overall glucose metabolism in normal man, 15 healthy subjects were infused with insulin for 8 h at sequential rates ranging from 0.2 to 5.0; each rate was used for 2 h. Glucose production and utilization were measured isotopically ([3-3H]glucose). Tissue insulin receptor occupancy was estimated from erythrocyte insulin binding. Glucose production was completely suppressed at plasma insulin concentrations of approximately 60 microunits/ml. Maximal glucose utilization (10-11 occurred at insulin concentrations of 200-700 microunits/ml. The concentration of insulin causing half-maximal glucose utilization (55 + 7 microunits/ml) was significantly greater than that required for half-maximal suppression of glucose production (29 +/- 2 microunits/ml, P less than 0.01). Maximal effects of insulin on glucose production and utilization occurred at plasma insulin concentrations causing 11 and 49% insulin receptor occupancy, respectively. The above dose-response relationships indicate that in man 1) glucose production is more sensitive to changes in plasma insulin concentration than is glucose utilization; 2) both hepatic and peripheral tissues may contain "spare" insulin receptors; and 3) relatively minor changes in plasma insulin concentration or insulin receptor function can cause appreciable alterations in glucose metabolism.

Original languageEnglish (US)
Pages (from-to)E630-639
JournalThe American journal of physiology
Issue number6
StatePublished - Jun 1981
Externally publishedYes

ASJC Scopus subject areas

  • Physiology (medical)


Dive into the research topics of 'Dose-response characteristics for effects of insulin on production and utilization of glucose in man.'. Together they form a unique fingerprint.

Cite this