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

TLDR

The study aimed to characterize how varying insulin doses affect glucose production, utilization, and overall metabolism in healthy adults. Insulin was infused at eight sequential rates (0.2–5.0 mU kg⁻¹ min⁻¹) for 2 h each, with glucose production and utilization quantified using [³H]glucose, and receptor occupancy inferred from erythrocyte insulin binding. Glucose production was fully suppressed at ~60 µU/ml insulin, whereas maximal utilization required 200–700 µU/ml; the half‑maximal utilization concentration (~55 µU/ml) was significantly higher than that for production (~29 µU/ml), indicating greater sensitivity of production to insulin, spare receptor capacity in both hepatic and peripheral tissues, and that modest insulin or receptor changes markedly alter glucose metabolism.

Abstract

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 mU.kg-1.min-1; 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 mg.kg-1.min-1) 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.